Tag: Microbiology (Bacteriology and fungi)

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* First public collection of bacteria from the intestine of mice

Mouse models are extensively used in pharmaceutical and medical research, and it is known that the communities of microbes in their intestine can have a significant impact on the research output. However, there is still insufficient information available about many bacteria inhabiting the intestine of mice. For the first time, a collection of cultured bacterial strains provides comprehensive information on the mouse gut microbiota: Scientists at the Technical University of Munich were able to isolate, characterize, and archive a hundred strains, including 15 hitherto unknown taxa.

They are microscopically small and live both on humans and animals. They can help with recovery from an illness or literally make you sick: Billions of micro-organisms, most of which are found in the intestines, as well as on the skin and other regions of the body, living in symbiosis with the host. These tiny beings are of central importance, and experts refer to them as intestinal microbiota or the microbiome. Decoding its characteristics and obtaining a better understanding of it is what scientists at the Central Institute for Nutrition and Food Research (ZIEL) at the Technical University of Munich (TUM) are working on.

76 cultured bacterial species from the mouse microbiome identified and archived

One key to obtaining information about the interactions between gut bacteria and their host are mouse models. However only a handful of mouse intestinal bacteria have been made publicly available and fully characterized so far. This is a highly limiting factor for research, because it complicates the annotation of data obtained by molecular techniques, and because it has been shown that gut microbiomes are to some extent specific to their host, and researchers have been using strains of other origin in mouse models. Dr. habil. Thomas Clavel from ZIEL and colleagues describe a new resource in “Nature Microbiology” which, for the first time, contains a hundred cultured bacterial strains from the mouse gut microbiome. For this study, 1500 cultures were examined, and 76 different species were identified and archived.

“The goal of our work was to take a big initial step towards decoding the cultured fraction of gut bacterial communities in mice. There is still a lot left to do. We will be making our work available to scientists around the world and hope that others will also help to find the pieces to complete the puzzle,” said Clavel, who has been researching various bacteria in gut microbiomes at the TU Munich for ten years. Although the mouse gut microbiome presents a number of similarities with the human microbiome, the work showed that around 20 percent of the strains in the collection prefer colonizing the intestines of mice.

In order to better understand colonization processes in the intestine, bacteria first need to be identified and characterized in detail. “Because mouse models are indispensable for preclinical studies, the resource now made available shall contribute to a better understanding of microbe-host interactions and to a higher degree of standardization,” said Clavel.

For the first time, the researchers were able to characterize new bacteria with important functional properties: For example Flintibacter butyricum produces the short-chain fatty acid butyrate from both sugars and proteins — a rare property in the realm of intestinal bacteria. Butyrate is a main product of fermentation in the intestine, and has been shown to have anti-inflammatory and positive effects against metabolic diseases in numerous studies.

“We still have a lot of gaps in our knowledge about gut microbiomes, but with the publicly available database of cultured mouse gut bacteria and their genetic material, we are now a little closer to our goal,” Thomas Clavel from the TUM stated enthusiastically.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160812103715.htm Original web page at Science Daily

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CRISPR gene-editing system unleashed on RNA

Researchers who discovered a molecular “scissors” for snipping genes have now developed a similar approach for targeting and cutting RNA. The new cutting tool should help researchers better understand RNA’s role in cells and diseases, and some believe it could one day be useful in treatments for illnesses from Huntington’s to heart disease.

To develop the “blades” for the process, researchers led by Feng Zhang at the Broad Institute used CRISPR (clustered regularly interspaced short palindromic repeats)—a system that bacteria evolved to fight off pathogens. CRISPR has previously been used to edit DNA but had been theorized to work on RNA as well.

The new findings, reported Thursday in Science, came from systematically exploring different aspects of that natural defense system that protects bacteria—and may eventually be put to use helping people. “Nature has already invented all these really interesting mechanisms,” Zhang says, comparing himself with a treasure hunter. “We’re just trying to play with that and learn how they work…then turn them into tools that will be useful to us.”

Zhang says the new paper will not affect an ongoing patent dispute over who owns rights to the gene-editing approach known as CRISPR–Cas9. His team was the first to use CRISPR–Cas9 in mammalian cells. Another team—led by Jennifer Doudna, at the University of California, Berkeley, and French researcher Emmanuelle Charpentier—was first to publish on CRISPR–Cas9, showing its activity in bacteria.

Ironically, Doudna was a co-author on a March paper in Cell that used CRISPR–Cas9 to cut RNA in mammalian cells whereas Zhang’s new paper focuses on bacteria. The two RNA manipulation methods may be complementary ways to approach the same ends or one may turn out to be more efficient than the other. In interviews this week each group praised the other’s work while touting the advantages of their own respective approaches.

Zhang says his new method—using the enzyme C2c2 to target RNA—relies on an existing natural system and therefore may be more effective than an approach that requires more manipulation. Gene Yeo, senior author on the Cell paper, says he has collaborated with both Doudna and Zhang, and described the new paper as a continuation of the kind of “friendly competition” that drives science. “There’s always a bit of a race between a lot of the groups, including mine,” he says. “I think scientific competition is good. People tend to push the boundaries more.”

Although Yeo pointed out that the C2c2 system has not yet been shown to work in mammalian cells, Zhang says unpublished results make him optimistic that it will.

Both RNA-targeting approaches have a long way to go before they could be tested in people—but the promise is there, says Yeo, a professor of cellular and molecular medicine at the University of California, San Diego. Targeting RNA may also offer new insights into how changes in RNA lead to changes in biology and the development of disease. “I think we’ll see an avalanche of these tools that will enable us to monitor and study RNA,” Yeo says. “This helps us think about RNA as not just an intermediate molecule between DNA and protein,” but as a therapeutic tool for treating diseases and problems of development.

Genes consist of double-stranded DNA, which makes single-stranded RNA—which in turn makes the proteins needed for life. Many diseases result from too much or too little protein. Theoretically, acting on the RNA could push those protein levels up or down, thereby offering treatments.

Manipulating RNA poses fewer ethical concerns than tinkering with the underlying DNA, although gene editing will remain a better approach for treating some diseases. “The problem with DNA editing is that it’s permanent,” Yeo says. “That could be good, but what if you make a mistake?” In some cases, such as with brain cells, DNA repair mechanisms are so strong that it may be more effective to act on the RNA rather than cutting the DNA, says Yeo, who has started a company that’s still in stealth mode to begin looking at treating diseases with this approach.

The Science paper reports that C2c2 could also be used to add fluorescent tags to RNA as a way to track and better understand its activities.

Zhang says he has long been interested in developing systems to target RNA. His team decided to survey the different kinds of CRISPR systems to figure out their functions. C2c2 turned out to be an RNA-targeting system, according to the new study, which includes researchers from the National Institutes of Health, Rutgers University and the Skolkovo Institute of Science and Technology in Russia, in addition to Harvard University and Massachusetts Institute of Technology. Like the Cas9 system that targets specific DNA, C2c2 can be aimed directly at desired RNA sequences, with seemingly few off-target effects. “The reason that it has evolved is to be able to use RNA guides to target RNA,” Zhang says.

His colleague, Eugene Koonin, a co-author on the new paper, puts it more poetically: “Evolution of life to a very large extent is a story of host–parasite interactions,” says Koonin, an expert in evolutionary genomics at the National Center for Biotechnology Information. “As we explore this arms race between host and parasite, we discover more and more intricate, novel ways in which cellular organisms cope with parasites and parasites counteract.”

Nature doi:10.1038/nature.2016.20030

https://www.sciencedaily.com/ Nature

http://www.nature.com/news/crispr-gene-editing-system-unleashed-on-rna-1.20030  Original web page at Nature

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New material kills E. coli bacteria in 30 seconds

Every day, we are exposed to millions of harmful bacteria that can cause infectious diseases, such as the E. coli bacteria. Now, researchers at the Institute of Bioengineering and Nanotechnology (IBN) of Agency for Science, Technology and Research (A*STAR), Singapore, have developed a new material that can kill the E. coli bacteria within 30 seconds. This finding has been published in the peer-reviewed journal, Small.

“The global threat of drug-resistant bacteria has given rise to the urgent need for new materials that can kill and prevent the growth of harmful bacteria. Our new antimicrobial material could be used in consumer and personal care products to support good personal hygiene practices and prevent the spread of infectious diseases,” said IBN Executive Director, Professor Jackie Y. Ying.

Triclosan, a common ingredient found in many products such as toothpastes, soaps and detergents to reduce or prevent bacterial infections, has been linked to making bacteria resistant to antibiotics and adverse health effects. The European Union has restricted the use of triclosan in cosmetics, and the U.S. Food and Drug Administration is conducting an on-going review of this ingredient.

Driven by the need to find a more suitable alternative, IBN Group Leader Dr Yugen Zhang and his team synthesized a chemical compound made up of molecules linked together in a chain. Called imidazolium oligomers, this material can kill 99.7% of the E. coli bacteria within 30 seconds aided by its chain-like structure, which helps to penetrate the cell membrane and destroy the bacteria. In contrast, antibiotics only kill the bacteria without destroying the cell membrane. Leaving the cell structure intact allows new antibiotic-resistant bacteria to grow.

“Our unique material can kill bacteria rapidly and inhibit the development of antibiotic-resistant bacteria. Computational chemistry studies supported our experimental findings that the chain-like compound works by attacking the cell membrane. This material is also safe for use because it carries a positive charge that targets the more negatively charged bacteria, without destroying red blood cells,” said Dr Zhang.

The imidazolium oligomers come in the form of a white powder that is soluble in water. The researchers also found that once this was dissolved in alcohol, it formed gels spontaneously. This material could be incorporated in alcoholic sprays that are used for sterilization in hospitals or homes.

E. coli is a type of bacteria found in the intestines of humans and animals, and some strains can cause severe diarrhea, abdominal pain and fever. Such infection is contagious and can spread through contaminated food or water, or from contact with people or animals. Good hygiene practices and proper food handling can prevent contamination.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160606101404.htm  Original web page at Science Daily

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Targeting metals to fight pathogenic bacteria

Researchers at the Laboratory for Molecular Infection Medicine Sweden (MIMS) at Umeå University in Sweden participated in the discovery of a unique system of acquisition of essential metals in the pathogenic bacterium Staphylococcus aureus. This research was led by scientists at the CEA in France, in collaboration with researchers at the University of Pau, the INRA and the CNRS. It represents a new potential target for the design of antibiotics. These results are being published in the journal Science on Friday 27 May.

Metals are necessary for life and pathogenic bacteria have developed elaborate systems to compensate for the low concentration of these essential metals in their environment, in particular within a host. The case of iron is particularly well documented with, in some bacteria, the production of molecules called siderophores that specifically capture iron in the medium. Researchers have now identified a new metal scavenging molecule produced in the bacterium Staphylococcus aureus and baptized it staphylopine.

The researchers highlighted the role of the key players that allow the pathogen to acquire a wide range of essential metals in the environment, such as nickel, zinc, cobalt, copper and iron. Three enzymes, whose functions were unknown so far, allow the production of staphylopine by the combination of three building blocks (D-histidine, amino butyrate and pyruvate). An export system expels staphylopine out of the cell where it traps the target metals from the extracellular medium. The staphylopine / metal duo can then be picked up by the cell via a specific import system. In the absence of these import / export systems, the virulence of Staphylococcus aureus was known to be reduced, although the origins of this phenomenon were not fully understood.

“Remarkably, a few years ago we found that many, taxonomically unrelated, bacteria can release high concentrations of a wide variety of D-amino acids to the environment. Therefore, D-histidine might be just one D-amino acid of many that could serve as a building block for novel staphylopine-like molecules,” explained Felipe Cava from MIMS/Umeå University.

The discovery of staphylopine, how it is built, and how it is transported by these systems could now lead the way for the development of a new strategy against pathogenic bacteria, by targeting their addiction to metals.

Surprisingly, staphylopine closely resembles nicotianamine, a molecule that is found in all plants and that ensures the transport of essential metals from the roots, where they are collected, to the various aerial organs. The discovery of a similar metal scavenger in the three kingdoms of life (archaea, eukaryotes and now bacteria) suggests an ancient origin for this type of molecule.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160526151937.htm Original web page at Science Daily

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Deadly fungus threatens African frogs

Misty mountains, glistening forests and blue-green lakes make Cameroon, the wettest part of Africa, a tropical wonderland for amphibians.

The country holds more than half the species living on the continent, including dozens of endemic frogs — an animal that has been under attack across the world by the pervasive chytrid fungus (Batrachochytrium dendrobatidis). Africa has been mostly spared from the deadly and rampant pathogen that wiped out entire species in Australia, Madagascar and Panama, until now.

University of Florida herpetologist David Blackburn and colleagues at the Museum für Naturkunde in Berlin have documented declines in frog species on Cameroon’s Mount Oku and Mount Manengouba over a span of more than 12 years. The scientists link the decline of at least five species of frogs found only in these mountains to chytrid, which may have been exacerbated by habitat destruction, pollution and climate change resulting in weaker and more susceptible frogs, said Blackburn, an associate curator of herpetology at the Florida Museum of Natural History on the UF campus.

“There’s been this perception that frogs in Africa are not affected by chytrid at all, but we have evidence of the disease in some animals,” said Blackburn, co-author of a new study appearing online this week in PLOS ONE. “This is the first real case of a decline across multiple amphibian species in Africa.”

Study scientists collected and documented abundance and diversity of frog species living on the two mountains before and after the immergence of chytrid in the area between 2008-2010. The persistent pestilence latches onto the frog’s skin and can spread internally to the animal’s organs, quickly leading to death.

Blackburn said many of the once common species, like the bright red Cardioglossa manengouba, a frog he discovered and named during graduate fieldwork in the early 2000s, are now scarce and nearly impossible to find.

“It’s looking like some of these frogs may not be around by the time my kids are old enough for me to take them to Cameroon to see them,” he said.

While chytrid is to blame for most of the patterns of decline in frogs worldwide, Blackburn said scientists have linked the fungus to climate change, which may drive the emergence of chytrid in some places.

In studies exploring declines of amphibians in Latin America, University of South Florida herpetologist Jason Rohr has shown that unpredictable climate fluctuations associated with climate change can increase chytrid-related die-offs.

“Our research has shown there may be an underappreciated link between climate change, disease and biodiversity losses,” Rohr said. “Global warming and the severity of unpredictable variations in temperature increase chytrid growth on amphibians.”

Blackburn said extreme temperature changes may affect the biology of the frogs by making them more, or less, susceptible to pathogens. He said this could easily be a factor in Cameroon, though he and colleagues have not yet collected enough data to make that call.

In captivity, frogs with chytrid are treated with an effective fungicide bath. In the Sierra Mountains of California, scientists have successfully released frogs inoculated with bacteria that make them less vulnerable to chytrid. But these methods are less practical in the mountains of Cameroon.

“Even if a cure was found, it would be hard to inoculate all of the individual frogs out there,” Backburn said. “Promoting a healthier environment in general for Africa’s amphibians in terms of water quality and habitat protection is our best shot for keeping these species around.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160506160130.htm  Original web page at Science Daily

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Superbug infections tracked across Europe

For the first time, scientists have shown that MRSA (methicillin-resistant Staphylococcus aureus) and other antibiotic-resistant ‘superbug’ infections can be tracked across Europe by combining whole-genome sequencing with a web-based system. In mBio, researchers at Imperial College London and the Wellcome Trust Sanger Institute worked with a European network representing doctors in 450 hospitals in 25 countries to successfully interpret and visualise the spread of drug-resistant MRSA.

MRSA and other superbugs are a life-threatening problem for all hospitals across Europe with an estimated 400,000 cases per year and 25,000 deaths from resistant, hospital-acquired infections.

To enable infection control teams across Europe to easily share information and to form a dynamic picture of the rise and spread of antibiotic-resistant bacteria, the scientists from the newly formed Centre for Genomic Pathogen Surveillance developed Microreact.org, a web-based visualisation and mapping tool.

Dr David Aanensen, head of the Centre for Genomic Pathogen Surveillance and joint lead author on the paper said: “Drug resistance is a growing problem both in Europe and across the world and doctors need fast and accurate information to stop epidemics. Our study demonstrates the potential for combining whole-genome sequencing with internet-based visualisation tools to enable public health workers and doctors to see how an epidemic is spreading and make swift decisions to end it.”

The research team read the whole genomes of S. aureus samples to identify which bugs are related to each other, and which are resistant to antibiotics. Using this approach, the scientists were not only able to show the rise and spread of MRSA across Europe, but also provide a quicker way to identify new hotspots of resistance.

Professor Hajo Grundmann, principal investigator on the study and Head of the Institute of Infection Prevention and Hospital Hygiene at the University Medical Centre Freiburg in Germany said: “One of the problems is that these bacteria not only spread within and between hospitals, but they also change their genetic properties due to evolutionary processes over time. Microreact.org allows us to look at their evolution within the context of how they are spreading across Europe.”

In the paper, the scientists show that combining the drug-resistance profile of a bacteria with its whole-genome DNA sequence allowed them to build up a series of drug-resistance ‘DNA photofits’ for resistance to specific drugs. In the future, such an approach may help doctors decide on the best treatments more quickly and help bring drug-resistant outbreaks to an end.

Professor Ed Feil, joint lead author from the Milner Centre for Evolution, at the University of Bath, said: “We’ve developed user-friendly analysis software that demonstrates how whole genome sequence data can be a powerful tool for pan-European surveillance of MRSA and other important pathogens.

Being able to track the spread of outbreaks across the whole continent allows policymakers to identify potential risks to public health and implement appropriate prevention and control strategies.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160505135015.htm Original web page at Science Daily

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Tuberculosis in mongoose driven by social communication behavior

Tuberculosis infection in mongoose driven by social communication behaviour. An emerging strain of tuberculosis (TB), closely related to human TB, has been killing banded mongoose in Northern Botswana in significant numbers.

This novel pathogen, Mycobacterium mungi, did not infect mongoose through a primary airborne or oral route as normally seen in TB disease in humans and animals. The mechanism of transmission, however, was unknown.

Now, a research team led by Kathleen Alexander, associate professor of wildlife conservation in Virginia Tech’s College of Natural Resources and Environment, reports discovery of the pathogen’s unique transmission route in a new issue of the American Society for Microbiology journal mBio.

Using a suite of molecular techniques to identify the presence of M. mungi-specific DNA and examination of mongoose tissues and cells, Alexander and her team have discovered that TB transmission in mongoose occurs in conjunction with social behavior.

As with many animals, such as dogs or even hyenas, mongoose use urine and anal gland secretions to communicate with other members of their species. However, in the mongoose, secretions from sick animals were found to be infected with the TB pathogen.

These secretions, once deposited in the environment, allow the pathogen to be transmitted when other mongoose investigate and sniff the scent marks. The pathogen is also spread when an infected mongoose places its scent directly on other mongoose in its troop.

Abrasions or injuries in the skin or nose provide the portal of entry for this novel TB pathogen to invade and infect the mongoose host. Smaller social groups are most threatened by the disease, the researchers report.

“Banded mongoose are a territorial species, and individuals within a troop may have little or no direct contact with mongoose in adjacent social groups, limiting the potential for directly transmitted pathogens like TB to spread through a population,” explained Alexander, an affiliate of the Fralin Life Science Institute, who discovered the novel strain of TB in 2010.

“But this TB pathogen circumvents the mongoose’s natural social barriers to infectious disease transmission by hijacking social communication behavior,” she said. “We keep being surprised by infectious disease-causing organisms and their ability to adapt to a particular environment, behaving, in some cases, dramatically differently than we expect.”

TB is an ancient disease that continues to be one of the most important health threats to humans, wildlife, and domestic animals globally.

The discovery by Alexander’s team of the novel mode of infection by M. mungi in banded mongoose has critical implications to our current understanding of tuberculosis infection dynamics, warranting further examination of other species where this transmission pathway may also occur, the researchers point out in their article.

Potential sources of pathogen exposure were evaluated, including soil, sewage, and human and mongoose feces, as well as feces from 16 different wildlife species — from elephants to domestic cows. Despite this, M. mungi DNA could only be found in banded mongoose tissues and secretions. The scientists examined 155 mongoose between July 2000 and June 2015, conducting in-depth studies of tissues from 79 of these animals.

TB lesions were found in a variety of organs, but more significantly in the nose, nasal cavity, and skin — those parts of the mongoose host in frequent contact with anal gland secretions and urine during olfactory communication behavior. Lung lesions were only found in affected animals in advanced stages of the disease.

“M. tuberculosis complex pathogens infect many species of domestic and wild animals as well as humans in the U.S. and across the globe,” noted Alexander. “Our findings have changed the way we must think about tuberculosis and infectious disease transmission in territorial species.”

“Mechanisms of host exposure are still not completely understood for many host species and M. tuberculosis complex organisms,” she continued. “There is an urgent need to better understand the processes that influence environmental transmission and persistence of TB pathogens and resultant disease control implications.”

Alexander noted, “We have recently sequenced the genome of this emerging pathogen, and we can now start to investigate why this TB pathogen behaves so differently — patterns that have important implications to our understanding of TB disease in both humans and animals.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160510160058.htm  Original web page at Science Daily

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* Infection alert system in catheters could tackle hospital superbugs

A new infection alert system in catheters could prevent serious infections in millions of hospital patients worldwide. The system, detailed in a new paper in Biosensors and Bioelectronics, changes the color of the urine so patients and carers can see easily if bacteria are starting to block the catheter.

The researchers who invented the new catheter infection alert, from the University of Bath, say it could help tackle these infections. It could also be beneficial for elderly people in care homes.

A catheter drains urine from the bladder when a person can’t release urine without help or is incontinent, including following anesthesia. 100 million urinary catheters are used around the world every year, but the infections they sometimes cause can be problematic for thousands of people. Hospital acquired urinary infections affect more than 90,000 patients a year in the US alone, according to the Centers for Disease Control and Prevention.

The new system designed by Dr. Toby Jenkins and his colleagues provides a means of early detection, so the catheter can be changed and the infection treated before a person becomes unwell.

“Catheter-related infections are a serious problem, especially if the bacteria are resistant to antibiotics. We hope that with this simple to use sensor system we can ultimately make a real difference to patients’ lives,” said Dr. Jenkins.

Over time bacteria can build a layer called a biofilm inside the catheter tubes that eventually blocks them. The urine can’t escape and pushes back into the kidneys where the bacteria can cause kidney failure, body-wide infection and death. Up to half of people who use catheters long-term have problems with blockages caused by bacteria, but there is currently no way to detect potential blockages before they cause problems.

The new coating detects biofilms built by a bacterium called Proteus mirabilis, the most common cause of catheter blockage. The system gives advanced warning of a catheter blockage 10 to 12 hours before it happens.

The coating is made up of two layers. The first reacts to changes in urine caused by the bacteria, the second layer releases the dye. The dyed urine gathers in the collection bag, turning the urine bright yellow. The color change reveals the infection.

Dr. Jenkins’ team used a glass bladder, artificial urine and bacteria from patient samples to test the system. It responds to changes in the acidity, or pH, of urine caused by bacteria. As bacteria multiply, the substances they release raise the pH so the urine becomes more alkaline than acidic. This change dissolves the top layer of the coating, releasing the super-bright dye held in the second layer.

The glass bladder tests showed that when there is no bacterial infection the dye stays in the second layer despite liquid constantly flowing past it.

Biofilms built by bacteria are not easy to treat. They avoid the natural defenses of the immune system and can’t be broken down by antibiotics. Dr. Jenkins is optimistic about the benefits of the system: “Our new coating works with existing catheter designs and gives a clear, early visual warning of infection before a catheter is blocked. It could dramatically reduce the number of infections resulting from bacterial blockages.”

The authors also hope the catheter coating could be used to cut the cost of treating infection, estimated to be £120 million a year in England and Wales. The next step is to test the coating using urine collected from volunteers and then ultimately to run a clinical trial to show the system is safe and beneficial for patients.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/04/160425095523.htm  Original web page at Science Daily

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Antibiotic resistance: it’s a social thing

Trace concentrations of antibiotic, such as those found in sewage outfalls, are enough to enable bacteria to keep antibiotic resistance, new research from the University of York has found. The concentrations are much lower than previously anticipated, and help to explain why antibiotic resistance is so persistent in the environment.

Antibiotic resistance can work in different ways. The research described the different mechanisms of resistance as either selfish or co-operative. A selfish drug resistance only benefits the individual cell with the resistance while a co-operative antibiotic resistance benefits both the resistant cell and surrounding cells whether they are resistant or not.

The researchers analysed a plasmid called RK2 in Escherichia coli, a bacterium which can cause infectious diarrhea. RK2 encodes both co-operative resistance to the antibiotic ampicillin and selfish resistance to another antibiotic, tetracycline. They found that selfish drug resistance is selected for at concentrations of antibiotic around 100-fold lower than would be expected — equivalent to the residues of antibiotics found in contaminated sewage outfalls.

The study, which is published in Antimicrobial Agents and Chemotherapy (AAC), involved Professor Michael Brockhurst, Dr Jamie Wood and PhD student Michael Bottery in the Departments of Biology and Mathematics at York.

Dr Wood said: “The most common way bacteria become resistant to antibiotics is through horizontal gene transfer. Small bits of DNA, called plasmids, contain the resistance and can hop from one bacteria to another. Worse still, plasmids often contain more than one resistance.”

Michael Bottery added: “There is a reservoir of antibiotic resistance out there which bacteria can pick and choose from. What we have found is some of that resistance can exist at much lower concentrations of antibiotic than previously understood.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160315090336.htm  Original web page at Science Daily

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New compounds discovered as candidates for new antimicrobial drugs against Listeria infection

Scientists at Umeå Centre for Microbial Research (UCMR) have discovered chemical compounds which are able to attenuate the virulence of the bacterial human pathogen Listeria monocytogenes. Their findings are published today in the high impact journal Cell Chemical Biology.

The dramatic increase of antibiotic resistance makes new antimicrobial strategies necessary. The researchers at Umeå University in Sweden are studying an alternative approach, to inhibit the disease capacity (virulence) of bacteria but not their viability. Compared with traditional antibiotics, which often kill the bacteria, the risk of resistance development in disarmed bacteria is lower, since their survival does not depend on resistance against the new drug.

A Listeria infection can be very severe, particularly among patients such as elderly, infants, immunocompromised or pregnant women. Although disease occurrence is relatively low, Listeria‘s severe and sometimes fatal health consequences make it among the most serious foodborne infections, with a mortality of 30%. Listeria is found in unpasteurized dairy products and various ready-to-eat foods, and can grow at refrigeration temperatures. In Sweden, 60-90 people per year get infected and the statistics show that the number of outbreaks is increasing.

The study involved several different Umeå University research groups with diverse specialties: Microbiology, Chemistry and Structural Biology. The group of Jörgen Johansson, professor at the laboratory for Molecular Infection Medicine Sweden (MIMS) and the Department of Molecular Biology collaborated with the research groups of Elisabeth Sauer-Eriksson and Fredrik Almqvist, both professors at the Department of Chemistry.

The researchers tested a large number of possible candidates, which could inhibit expression of the Listeria virulence factors. For the test, they screened Listeria infection of human cells with a collection of ring-fused 2-pyridones. The scientists could prove that the ring-fused 2-pyridones could both attenuate the uptake of Listeria in the cell and the activity of the virulence regulator PrfA, which control the pathogenic abilities of Listeria.

The researchers also identified the first crystal structure of PrfA together with an inhibitor. Binding of the inhibitor to PrfA blocked its ability to interact with DNA, thereby preventing expression of virulence factors. As a consequence, Listeria bacteria were not able to bind and infect the human cells.

“This study means a lot for future development of ‘disarming compounds’, not only in Listeria. In fact, our study is the first example on a structural level of an inhibition of any virulence regulator in bacteria,” says Jörgen Johansson about the impact of the findings.

“The first results are very promising. We have been able to use the structural information to design and synthesize new improved candidates that are now being evaluated,” added Fredrik Almqvist.

“We now know that this class of compounds (2-pyridones) constitute a great platform for the development of virulence blocking compounds. We have developed methods that allow us to fine-tune the substitution pattern and compound properties in such a way that we can direct these compounds towards several different pathogens e.g. E. coli and Chlamydia. And more studies are ongoing with other pathogens,” adds Fredrik Almqvist.

“Through this very fruitful research collaboration, we showed that Umeå has all the tools and expertise needed to understand and develop new antimicrobial strategies,” says Elisabeth Sauer-Eriksson.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160317151130.htm  Original web page at Science Daily

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Botulism in waterbirds: Mortality rates and new insights into how it spreads

Outbreaks of botulism killed large percentages of waterbirds inhabiting a wetland in Spain. During one season, more than 80 percent of gadwalls and black-winged stilts died. The botulinum toxin’s spread may have been abetted by an invasive species of water snail which frequently carries the toxin-producing bacterium, Clostridium botulinum, and which is well adapted to wetlands polluted by sewage. Global warming will likely increase outbreaks, said corresponding author Rafael Mateo, PhD. The research was published March 25th in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

Botulism is a major killer of waterbirds, including some endangered species. In earlier studies, some also published in Applied and Environmental Microbiology, these investigators had found that eutrophication of some of these wetlands, due to effluent from waste water treatment plants, was encouraging growth of C. botulinum and other bacterial pathogens of birds.

In the current study, the investigators surveyed mortality among the resident waterbirds, and investigated how the bacterium is spread. During two outbreaks, the investigators collected 43 dead white-headed ducks, representing seven percent and 17 percent of their maximum population on Navaseca lake during 2011 and 2012, respectively, said Mateo, who is Head of the Group of Wildlife Toxicology, at the Spanish Institute of Game and Wildlife Research, Cuidad Real, Spain. White-headed ducks are highly endangered, with only about ten thousand surviving individuals worldwide.

Additionally, the team found death rates of greater than 80 percent among gadwalls and black-winged stilts in 2011. Mortality estimates for white-headed ducks are probably low, said Mateo, explaining that scavengers frequently devour dead birds, and that it is difficult to find ailing or expired avians in the dense vegetation along the lake shore.

The team also investigated how the disease spreads. The main source of spread, previously known, is the “carcass-maggot cycle,” said Mateo. “Birds feed on maggots growing in a carcass containing C. botulinum and its neurotoxin,” and then die, with the cycle beginning anew as the dead birds become food for more maggots. “The spread of the outbreak is exponential,” said Mateo.

Additionally, the investigators found that 30 percent of an invasive species of freshwater snail, collected during outbreaks, carried C. botulinum. These snails, Physa acuta, are an invasive species that is well adapted to wetlands polluted by sewage. They are likely sources of food for a number of different waterbird species, including mallards, gulls, and coots, said Mateo.

Differences in diets result in different levels of vulnerability among bird species. Flamingos and grebes appeared untouched by outbreaks, likely because they appear to feed mainly on prey species that do not carry C. botulinum, such as certain crustaceans, and/or possibly because they are more resistant genetically than other species to this pathogen.

Mateo warned that outbreaks would likely occur more frequently due to global warming. In earlier research, also published in Applied and Environmental Microbiology, his group showed that higher summer temperatures are associated with higher mortality rates among waterbirds during outbreaks. “We have observed that outbreaks occur when the mean temperature in July exceeds 26˚C [79˚F.],” he said. Additionally, when water is scarce due to drought, wetlands eutrophy more frequently, which favors anaerobic bacteria such as C. botulinum. Finally, birds tend to concentrate in the few wetlands that are maintained with treated sewage, which boosts mortality from botulism and other diseases, he said.

These wetlands, which are located in La Mancha, which was made famous by the novel, Don Quixote, and which are rich in biodiversity, are a UNESCO “biosphere reserve.” Their unique habitat is important for many bird species, including migratory birds that breed there, such as the afore-mentioned white-headed duck. But outbreaks of botulism are common. “We wanted to characterize the ecology of the avian botulism in these wetlands to know to what degree human action–notably poor treatment of sewage–was determining the outbreaks’ occurrence,” said Mateo.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160325151729.htm  Original web page at Science Daily

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Study finds vast diversity among viruses that infect bacteria

Viruses that infect bacteria are among the most abundant life forms on Earth. Our oceans and soils, and potentially even our own bodies, would be overrun with bacteria were it not for bacteria-eating viruses–called bacteriophages–that keep the microbial balance in check. Now, a new study suggests that bacteriophages made of RNA — a close chemical cousin of DNA — likely play a much larger role in shaping the bacterial makeup of worldwide habitats than previously recognized. Viruses that infect bacteria are among the most abundant life forms on Earth. Our oceans and soils, and potentially even our own bodies, would be overrun with bacteria were it not for bacteria-eating viruses–called bacteriophages–that keep the microbial balance in check.

Now, a new study at Washington University School of Medicine in St. Louis suggests that bacteriophages made of RNA — a close chemical cousin of DNA — likely play a much larger role in shaping the bacterial makeup of worldwide habitats than previously recognized.

The research, publishing on March 24 in the Open Access journal PLOS Biology, identifies 122 new types of RNA bacteriophages in diverse ecological niches, providing an opportunity to define their contributions to ecology, and potentially to fight bacterial infections, particularly those resistant to antibiotics.

“Lots of DNA bacteriophages have been identified, but there’s an incredible lack of understanding about RNA bacteriophages,” explained senior author David Wang, PhD, associate professor of molecular microbiology. “They have been largely ignored — relatively few were known to exist, and for the most part scientists haven’t bothered to look for them. This study puts RNA bacteriophages on the map and opens many new avenues of exploration.”

Wang estimates that of the more than 1,500 bacteriophages that have been identified, 99 percent of them have DNA genomes. The advent of large-scale genome sequencing has helped scientists identify DNA bacteriophages in the human gut, skin and blood as well as in the environment, but few researchers have looked for RNA bacteriophages in those samples.

First author Siddharth Krishnamurthy and the team, including Dan Barouch, MD, PhD, Beth Israel Deaconess Medical Center and Harvard Medical School, identified RNA bacteriophages by analyzing data from oceans, sewage, soils, crabs, sponges and barnacles, as well as insects, mice and rhesus macaques.

RNA bacteriophages have been shown to infect gram-negative bacteria, which have become increasingly resistant to antibiotics and are the source of many infections in health care settings. But the researchers also showed for the first time that these bacteriophages may also infect gram-positive bacteria, responsible for strep and staph infections as well as MRSA.

“What we know about RNA bacteriophages in any environment is limited,” Wang said. “But you can think of bacteriophages and bacteria as having a predator-prey relationship. We need to understand the dynamics of that relationship. Eventually, we’d like to manipulate that dynamic to use phages to selectively kill particular bacteria.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160324145402.htm  Original web page at Science Daily

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Fungal pathogen sheds gene silencing machinery and becomes more dangerous

For more than a decade, a rare but potentially deadly fungus called Cryptococcus deuterogatti has taken up residence in the Pacific Northwest and Vancouver Island. Unlike its cousin Cryptococcus neoformans, which mostly infects patients with compromised immune systems, this fungus has sickened hundreds of otherwise healthy people.

Now, researchers have found that the pathogen tossed aside over a dozen different genes on its way to becoming a new, more virulent species. Surprisingly, most of these discarded genes play a part in RNA interference or RNAi, a defense mechanism employed by fungi and other organisms to protect the integrity of their genomes. The study was published March 4 in PLOS Genetics.

“Genome instability is a bad thing in terms of human health, because it is linked to cancer and other diseases,” said Blake Billmyre, lead study author and a graduate student in Joseph Heitman’s lab at Duke University School of Medicine. “But it could be good thing for single-celled organisms like Cryptococcus, because it enables them to mutate, evolve and adapt to survive under different conditions.”

Cryptococcus deuterogatti was largely confined to tropical climates until 1999, when it showed up on Vancouver Island and began spreading throughout southwest Canada and into Washington and Oregon. The emerging fungal pathogen causes severe pulmonary and central nervous system infections, and is fatal if left untreated.

Five years ago, researchers in the Heitman lab participated in an international collaborative consortium to sequence the genome of this outbreak species and discovered that it had lost two genes involved in RNAi, a process previously thought to be key to its survival.

The RNAi gene-silencing machinery normally shreds the genetic instructions for harmful viruses or silences rogue genes that might contaminate the fungus’ genome. But Cryptococcus deuterogatti had holes in its genome where the two RNAi genes should have been.

Armed with this information, Billmyre hypothesized that other genes in this missing set of genes might also function in RNAi. He and his colleagues compared the genomes of Cryptococcus deuterogatti with less potent cousins like Cryptococcus neoformans, which predominantly infects immunocompromised individuals. They found that C. deuterogatti has lost 14 genes compared to the other, less pathogenic, species.

The researchers then conducted a number of genetic and molecular analyses to determine if any of these lost genes played a role in RNAi. They mutated each of the genes in Cryptococcus neoformans, which has fully functioning RNAi machinery, to see if these genes were needed for the fungi to silence extra genetic material.

Joseph Heitman, the James B. Duke professor and chair of Molecular Genetics and Microbiology, said he expected to find maybe one or two other genes involved in RNAi. To his surprise, they found that 11 of the 14 missing genes they surveyed were involved in gene silencing.

“We could have imagined that the species lost a couple of RNAi genes, and then a smattering of genes involved in all other kinds of processes,” said Heitman. “Instead, the one glaring difference between these more and less virulent species seems to be the loss of the RNAi pathway.”

Though the researchers don’t know why shedding the RNAi machinery could help Cryptococcus assume a deadlier form, they do have some ideas. It could enable the fungi to cohabitate with killer viruses that pump out powerful toxins to poison competing organisms. Or it could allow them to accumulate mutations or even extra chromosomes to gain resistance against antifungal medications.

Whatever the reason, the discovery could pave the way for future studies using comparative genomics to identify other sets of related genes. Once one gene in a pathway is lost, the researchers hypothesize that an organism can find itself on a slippery evolutionary slope as other genes that are no longer of benefit are lost in quick succession. Only a few other examples of this system-wide pattern of gene loss, called systems polymorphisms, have been described so far.

“There is so much you can learn from looking for things that are missing,” said Billmyre. “It’s true what they say, you don’t know what you’ve got ’till it’s gone.”

https://www.sciencedaily.com/   Science Daily

https://www.sciencedaily.com/releases/2016/03/160304160348.htm  Original web page At Science Daily

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Investigators trace emergence and spread of virulent salmonella strain

Since it first emerged more than half a century ago, a particular strain of multidrug-resistant Salmonella has spread all over the world. Now researchers have figured out why this strain, Salmonella Typhimuriam DT104, has been so successful. This new knowledge could prove valuable in combating other successful pathogens, according to the authors. The study is published ahead of print March 4th in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

In order to construct the history of this strain, the investigators performed whole-genome sequencing of samples of DT104 that had been collected from patients over more than 40 years, from 1969 to 2012, in 21 countries, on six continents. Very tiny changes in the genome that took place over time enabled them to construct the strain’s family tree (which scientists call a phylogenetic tree). The sequences have also made it easy to estimate roughly when the pathogen acquired the resistance genes.

DT104’s success was due in no small part to its resistance to at least five antibiotics, including ampicillin, chloramphenicol, streptomycin, sulphonamide, and tetracycline, said corresponding author, Pimlapas Leekitcharoenphon, PhD.

Further abetting its spread, unlike other strains of DT Salmonella, DT104 was able to infect numerous livestock species, including cattle, poultry, pigs, and sheep, said Leekitcharoenphon. “Having multiple hosts increases the chances of dissemination,” she explained. Leekitcharoenphon is a postdoctoral researcher at the Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Lyngby.

Using a program that took into account the rate of mutations in DT104, the investigators estimated that it first emerged in 1948 as an antibiotic susceptible pathogen. It is not clear exactly when DT104 first acquired the multidrug resistance-containing transposon. Transposons are mobile genetic elements that can carry antibiotic resistance genes, and that can jump from one genome to another. In the case of DT104, transposons have been identified as the sources of the resistance genes. The study suggests that the first acquisition of antibiotic resistance may have happened in 1972. However, multidrug-resistant DT104 was first reported in 1984 in the United Kingdom.

The new results also illuminated, for the first time, the results of a program in Denmark to eradicate all pigs infected with DT104, which had begun in 1996, but was stopped in 2000 due to financial pressures. It turns out that program was quite successful.

“If we know and understand the past, we might be able to solve the current resistance problems and prevent future ones,” said Leekitcharoenphon.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/03/160304163407.htm  Original web page at Science Daily

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* What makes a bacterial species able to cause human disease?

An international team of scientists, led by researchers at University of California, San Diego School of Medicine and the J. Craig Venter Institute (JCVI), have created the first comprehensive, cross-species genomic comparison of all 20 known species of Leptospira, a bacterial genus that can cause disease and death in livestock and other domesticated mammals, wildlife and humans.

The findings are published in the February 18 online issue of PLOS Neglected Tropical Diseases. The resulting analyses reveal novel adaptations and traits in infectious species of Leptospira that not only help illuminate its evolutionary history, but may also provide new preventive and treatment approaches. The data comes from representative Leptospira strains obtained from four international labs and isolated from 12 countries. The work involved researchers at Yale University, UCLA, Cornell University and institutions in Australia, France, England, The Netherlands, Canada, Uruguay, Brazil, Peru and Thailand.

“Leptospira is the most complex genus of bacteria that infects humans,” said Joseph M. Vinetz, MD, professor of medicine and director of the UC San Diego Center for Tropical Medicine and Travelers Health. “This work compares the complete genome sequences of all known species of Leptospira to discover which genes make this bacterium a pathogen. It provides a roadmap for future research, including finding new ways to diagnose infection and vaccine development.”

This project was initiated and led by first author Derrick Fouts, PhD, JCVI associate professor. “The bioinformatics tools have matured to the point that we can now find the proverbial ‘needle in a haystack,’ meaning we can now identify genes and pathways that are unique to pathogenic microbes, which will focus future research efforts on these key pathogen-specific features,” Fouts said.

JCVI president Karen E. Nelson, PhD, who helped coordinate the initial phase of the project points out that the success of this study was based, in part, on the dedication and excitement of the Leptospira research community. “The comprehensive nature of this study serves as a model for emerging infectious diseases.”

Some species of Leptospira are non-infectious, deriving nourishment from dead or decaying organic matter. Other species are infectious with different, sometimes dire, consequences. In infected rats and mice, for example, the bacterium colonizes in the kidneys, but does not produce disease symptoms. In livestock, such as cattle, sheep, horses and pigs, and companion animals, such as dogs, leptospirosis may cause acute kidney, liver and lung damage and provoke fetal loss.

Humans can become infected with leptospirosis in ways similar to animals, through direct contact or ingestion or inhalation of contaminated water or soil. Humans are also vulnerable through direct contact with the urine of infected animals.

In infected humans, the disease provokes a range of effects. It may result in asymptomatic infection, mild, flu-like symptoms or jaundice, or lead to severe damage of the liver, kidney or central nervous system — and death. Globally, leptospirosis is the most important bacterial disease transmitted from animals to humans, with more than 1 million cases annually and 60,000 deaths.

Examples of Leptospira pathogen-specific features identified in the PLOS study include:

  • Discovery of proteins unique to pathogenic Leptospira that will accelerate vaccine development in humans, dogs, and livestock
  • Key adaptations of infectious Leptospira to mammals, such as biosynthesis of sialic acid, a type of sugar that allows these organisms to hide within the body so as to avoid destruction and which allows disease to progress
  • Infectious Leptospira evolutionarily acquired the ability to synthesize vitamin B12 from a simple amino acid precursor, which non-infectious Leptospira cannot

“One fascinating finding was discovering the CRISPR-Cas genetic machinery only in pathogenic Leptospira, but not in the intermediate or non-infectious groups of the genus. The evolutionary acquisition of novel CRISPR elements, which are only in pathogenic Leptospira, probably hastened adaptation to human infection. The significance of this observation remains to be explored,” said Vinetz.

CRISPR-Cas is a molecular immune system that confers resistance to foreign genetic elements, and provides a form of acquired immunity. Recent biotechnological advances have made it possible to alter the germline of many species, including mammals and disease-carrying mosquitoes, through CRISPR.

Vinetz said the next step will be to begin exploiting the genomic information “for vaccine and diagnostics development, experimental approaches to understanding mechanisms of disease pathogenesis and how Leptospira persist in the environment, all critical for developing new public health interventions aimed at reducing the global impact of this important but neglected zoonotic disease.”

https://www.sciencedaily.com/  Science Dai

https://www.sciencedaily.com/releases/2016/02/160218145135.htm  Original web page at Science Daily

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Mental abilities are shaped by individual differences in the brain

Everyone has a different mixture of personality traits: some are outgoing, some are tough and some are anxious. A new study suggests that brains also have different traits that affect both anatomical and cognitive factors, such as intelligence and memory.

“A major focus of research in cognitive neuroscience is understanding how intelligence is shaped by individual differences in brain structure and function,” said study leader Aron K. Barbey, University of Illinois neuroscience professor and Beckman Institute for Advanced Science and Technology affiliate.

For years, cognitive neuroscientists have tried to find relationships between specific areas of the brain and mental processes such as general intelligence or memory. Until now, researchers have been unable to successfully integrate comprehensive measures of brain structure and function in one analysis. Barbey and his team measured the size and shape of features all over the brain.

“We were able to look at nerve fiber bundles, white-matter tracts, volume, cortical thickness and blood flow,” said Patrick Watson, a postdoctoral researcher at the Beckman Institute and first author of the paper. “We also were able to look at cognitive variables like executive function and working memory all at once.”

Using a statistical technique called independent component analysis, the researchers grouped measures that were related to each other into four unique traits. Together, these four traits explained most of the differences in the anatomy of individuals’ brains. The traits were mostly driven by differences in brain biology, including brain size and shape, as well as the individual’s age. The factors failed to explain differences in cognitive abilities between people. The researchers then examined the brain differences that were unexplained by the four traits. These remaining differences accounted for the individual differences in intelligence and memory.

“We were able to identify cognitive-anatomical characteristics that predict general intelligence and account for individual differences in a specific brain network that is critical to intelligence, the fronto-parietal network,” Barbey said.

The four traits reported in this study are a unique way to examine how brains differ between people. This knowledge can help researchers study subtle differences linked to cognitive abilities, Watson said.

“Brains are as different as faces, and this study helped us understand what a ‘normal’ brain looks like,” Watson said. “By looking for unexpected brain differences, we were able to home in on parts of the brain related to things like memory and intelligence.”

The researchers released their data to the public through an online platform called Open Science Framework to encourage comprehensive studies of brain structure and function.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/02/160225153817.htm  Original web page at Science Daily

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New experimental test detects signs of Lyme disease near time of infection

When it comes to early diagnosis of Lyme disease, the insidious tick-borne illness that afflicts about 300,000 Americans annually, finding the proverbial needle in the haystack might be a far easier challenge — until now, perhaps. An experimental method developed by federal and university researchers appears capable of detecting the stealthy culprit Lyme bacteria at the earliest time of infection, when currently available tests are often still negative.

The team suggests the approach might also be useful for early detection of other elusive bacterial infections. The collaborators — from the National Institute of Standards and Technology (NIST), Institute for Bioscience and Biotechnology Research, and Johns Hopkins School of Medicine — recently reported the successful first trial of their new method.

“Our hypothesis was that Lyme bacteria shed vesicle-like particles — or fragments — derived from the cell wall of the bacteria circulating in the serum of individuals. These particles would contain membrane proteins that can be detected to provide a unique indicator of infection,” explains NIST research chemist Larik Turko.

The challenge was to detect these bacterial membrane proteins among the far, far more plentiful proteins normally present in serum, the watery, cell-free component of blood. The researchers speculated that running serum samples through a high-speed centrifuge — a standard step in chemistry labs — might selectively concentrate the larger, heavier fragments containing the bacterial membrane proteins into pellets. In effect, they predicted, this step would separate the wheat — the sparse target proteins — from the chaff — the much more abundant human serum proteins.

The new method’s promise was demonstrated in tests on serum samples drawn from three patients with undetected Lyme disease at the time of their initial doctor visit. By customizing standard analytical techniques for determining the types and amounts of chemicals in a sample, the team detected extremely small amounts of the target protein in all three samples. For chemistry buffs, the protein in enriched samples was present at a level of about four billionths of a millionth of a mole, the standard unit for amount of substance.

In one patient, the experimental method detected the bacteria three weeks before infection was confirmed with the standard blood tests now used. For the other two, infection was detected simultaneously by the two methods.

“The complexity of Lyme disease, combined with lack of biomarkers to measure infection, has slowed progress,” study collaborator John Aucott, head of the Johns Hopkins Lyme Disease Clinical Research Center.. “Now, thanks to recent advances in technology, the tiniest concentration of blood molecules can now be detected, molecules that were previously ‘invisible’ to scientists.”

Aucott will feature the joint study as an example in his 2016 AAAS Annual Meeting presentation, Big Data Clinical Realities and the Human Dimensions of Interoperable Data.

The current standard blood test for Lyme disease exposes the infection only after antibodies have accumulated to detectable levels, which can take up to 4 to 6 weeks. If patients exhibit a telltale bull’s-eye rash, diagnosis and treatment can begin earlier. But the rash does not occur in 20 to 30 percent of Lyme disease patients, according to the Centers for Disease Control and Prevention.

Rather than waiting for an infected person’s immune system to produce noticeable amounts of antibodies, the team chose to home in on the bacteria itself — specifically, proteins the bug sheds when attacked by the body’s defenses.

“From many candidates, we chose one that is both easily distinguished from human serum proteins and an unambiguous indicator of the bacteria,” Turko says. “This protein, which resides on the outer surface of membranes, became the target of our search in serum samples.”

But finding that target required an important preliminary step to ensure the accuracy of their measurements: making a reference sample that contained ample amounts of the target protein. With the reference sample, the team established the unmistakable signature the bug’s outer-surface membrane protein would yield when they examined samples drawn from patients. As a result of these steps, the team could detect the copies of the target protein, even though human proteins were 10 million times more plentiful.

“We believe that this approach may be universally applicable to detection of other bacterial infections in humans,” the researchers write.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/02/160212163919.htm  Original web page at Science Daily

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* Are we losing the fight against antibiotic resistance?

Tackling antibiotic resistance on only one front is a waste of time because resistant genes are freely crossing environmental, agricultural and clinical boundaries, new research has shown.

Analysis of historic soil archives dating back to 1923 has revealed a clear parallel between the appearance of antibiotic resistance in medicine and similar antibiotic resistant genes detected over time in agricultural soils treated with animal manure.

Collected in Denmark — where antibiotics were banned in agriculture from the 1990s for non-therapeutic use — the soil archives provide an ‘antibiotic resistance timeline’ that reflects resistant genes found in the environment and the evolution of the same types of antibiotic resistance in medicine.

Led by Newcastle University, UK, the study also showed that the repeated use of animal manure and antibiotic substitutes can increase the capacity of soil bacteria to mobilise, or ready themselves, and acquire resistance genes to new antibiotics.

Publishing their findings in the academic journal Scientific Reports, the study’s authors say the data highlights the importance of reducing antibiotic use across all sectors if we are to reduce global antibiotic resistance.

Lead author David Graham, Professor of Ecosystems Engineering at Newcastle University, said: “The observed bridge between clinical and agricultural antibiotic resistance means we are not going to solve the resistance problem just by reducing the number of antibiotics we prescribe in our GP clinics.

“To reduce the global rise in resistance we need to reduce use and improve antibiotic stewardship across all sectors.

“If this is not done, antibiotic resistance from imprudent sectors will cross-contaminate the whole system and we will quickly find ourselves in a situation where our antibiotics are no longer effective.”

Antibiotics have been used in medicine since the 1930s, saving millions of lives. Two decades later they were introduced into agricultural practices and Denmark was among the leaders in employing antibiotics to increase agricultural productivity and animal production.

However, a growing awareness of the antibiotic resistance crisis and continued debate over who and which activities are most responsible led to the EU calling for the use of antibiotics in non-therapeutic settings to be phased out and Denmark led the way.

The Askov Long-Term Experiment station in Denmark was originally set up in 1894 to study the role of animal manure versus inorganic fertilisers on soil fertility.

Analysing the samples, the team — involving experts from Newcastle University, the University of Strathclyde and Aarhus University — were able to measure the relative abundance of specific β-lactam antibiotic resistant genes, which can confer resistance to a class of antibiotics that are of considerable medical importance.

Prior to 1960, the team found low levels of the genes in both the manured soil and that treated with inorganic fertiliser. However, by the mid 1970’s, levels of selected β-lactam genes started to increase in the manured soils, with levels peaking in the mid 1980’s. No increase or change was detected in the soil treated with inorganic fertiliser.

“We chose these resistant genes because their appearance and rapid increase in hospitals from 1963 to 1989 is well-documented,” explains Professor Graham.

“By comparing the two timelines, we saw the appearance of each specific gene in the soil samples was consistent with the evolution of similar types of resistance in medicine. So the question now is not which came first, clinical or environmental resistance, but what do we do about it?”

Following the ban on non-therapeutic antibiotic use in Danish agriculture, farmers substituted metals for antibiotics, such as copper, and levels of the key β-lactam genes in the manured soils declined rapidly, reaching pre-industrialisation levels by 2010.

However, at the same time the team measured a 10-fold rise in Class 1 Integrons. These are gene carrier and exchange molecules — transporters which allow bacteria to readily share genes, including resistance genes.

These findings suggest the application of manure and antibiotic substitutes, such as copper, may be ‘priming’ the soils, readying them for increased resistance transmission in the future.

“Once antibiotics were banned, operators substituted them with copper which has natural antibiotic properties,” explains Professor Graham.

“More research is needed but our findings suggest that by substituting antibiotics for metals such as copper we may have increased the potential for resistance transmission.

“Unless we reduce use and improve stewardship across all sectors — environmental, clinical and agricultural — we don’t stand a chance of reducing antibiotic resistance in the future.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/02/160216143053.htm  Original web page at Science Daily

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* Researchers identify new Borrelia species that causes Lyme disease

Mayo Clinic researchers, in collaboration with the Centers for Disease Control and Prevention (CDC) and health officials from Minnesota, North Dakota and Wisconsin, have discovered a new bacterial species that causes Lyme disease in people. The new species has been provisionally named Borrelia mayonii. Prior to this finding, the only species believed to cause Lyme disease in North America was Borrelia burgdorferi.

In the paper published recently in The Lancet Infectious Diseases, Mayo Clinic scientists tested samples from U.S. patients from 2003 to 2014 for evidence of Lyme disease using a method called polymerase chain reaction (PCR). From 2012 to 2014, the researchers noticed unusual test results from 6 of 9,000 samples from residents of Minnesota, North Dakota and Wisconsin.

“Using a laboratory-developed test with a method called ‘melting temperature analysis,’ we detected six specimens that produced a PCR result that was clearly different from B. burgdorferi,” says Bobbi Pritt, M.D., director of the Clinical Parasitology Laboratory at Mayo Clinic who is first author of the study. “Mayo Medical Laboratories, the reference laboratory at Mayo, has tested more than 100,000 patient samples from all 50 states over the past decade using our PCR assay, but we’ve only recently detected evidence of B. mayonii.”

Based on these findings, the researchers believe that the organism may have only recently emerged in the upper Midwestern U.S. “It is possible that this species has been present for even longer but at such low levels that it escaped detection,” adds Dr. Pritt.

As with B. burgdorferi, researchers believe that B. mayonii is transmitted to humans by the bite of an infected black-legged tick (otherwise known as the deer tick). Typical symptoms of Lyme disease include fever, headache, rash, neck pain, and arthritis in later stages. Unlike B. burgdorferi, however, B. mayonii causes an illness that appears to be associated with nausea and vomiting, diffuse rashes (rather than a single bull’s-eye rash), and a higher concentration of bacteria in the blood.

Patients infected with B. mayonii will test positive for Lyme disease with currently available U.S. Food and Drug Administration-cleared Lyme disease tests. In some instances, B. mayonii bacteria also may be seen on a blood smear. “Specific identification of the organism can be made by using the Mayo Clinic PCR test, which detects the DNA of the Lyme disease bacteria,” notes Dr. Pritt.

For treatment, the patients described in the study fully recovered using antibiotics commonly used to treat Lyme disease caused by B. burgdorferi. The CDC recommends that health care providers who are caring for patients infected with B. mayonii also follow the antibiotic regimen described by the Infectious Diseases Society of America.

Dr. Pritt adds, “At this time, there is no evidence that B. mayonii is present outside of the Upper Midwest. However, the public should continue to take the recommended precautions against tick bites, as Lyme disease and other tick-borne diseases are well-established in much of the Northeast.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2016/02/160208135440.htm  Original web page at Science Daily

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Invasive amphibian fungus could threaten U.S. salamander populations

A deadly fungus causing population crashes in wild European salamanders could emerge in the United States and threaten already declining amphibians, according to a report released today by the U.S. Geological Survey.

The Department of the Interior is working proactively to protect the nation’s amphibians. The USG report released today highlights cooperative research and management efforts needed to develop and implement effective pre-invasion and post-invasion disease-management strategies if Batrachochytrium salamandrivorans (Bsal) enters and affects salamanders within the United States. Last week the United States Fish and Wildlife Service published a rule listing 201 salamander species as injurious under the Lacey Act, which will reduce the likelihood of introduction of Bsal into the country.

Although Bsal has not yet been found in wild U.S. salamander populations, scientists caution it is likely to emerge here because of the popularity of captive salamanders as household pets, in classrooms and in zoos; the captive amphibian trade is a known source of salamanders afflicted with the fungus.

Amphibians are the most endangered groups of vertebrates worldwide, with another fungus closely related to Bsal (Bd) contributing to amphibian die-offs and extinctions global over the last two decades.

“Based on the kinds of species affected and the fact that the United States has the highest salamander diversity in the world, this new pathogen is a major threat with the potential to exacerbate already severe amphibian declines,” said Evan Grant, a USGS wildlife biologist and lead author of the USGS report. “We have the unusual opportunity to develop and apply preventative management actions in advance.”

Bsal was first identified in 2013 as the cause of mass wild salamander die-offs in the Netherlands and Belgium. Captive salamander die-offs due to Bsal have occurred in the United Kingdom and Germany. Scientists believe Bsal originated in Asia and spread to wild European populations through the import and export of salamanders.

The USGS brought together scientists and managers from federal and state agencies that oversee resource conservation and management to identify research needs and management responses before Bsal arrives and becomes entrenched in the country. USGS, the USFWS, U.S. Forest Service, U.S. Department of Defense, National Park Service, zoos, and U.S. and international universities participated in the Bsal workshop.

Key findings in the report include:

  • Bsal is highly likely to emerge in U.S. populations of wild salamanders through imports of potentially infected salamanders.
  • Management actions targeted at Bsal containment after arrival in the United States may be relatively ineffective in reducing its spread.
  • A coordinated response, including rapid information sharing, is necessary to plan and respond to this potential crisis.
  • Early detection of Bsal at key amphibian import locations, in high-risk wild populations, and in field-collected samples is necessary to quickly and effectively implement management responses.

“The increasing pace of global commerce and emergence of new infectious diseases put vulnerable native wildlife populations at risk for extinction,” said Grant. “Managing disease threats to the 191 species of U.S. salamanders is essential for the global conservation of salamanders.”

Grant noted that the process by which Bsal research and management needs were identified could be adapted for future infectious disease threats to wildlife.

The workshop and Open-File Report were supported by the USGS Amphibian Monitoring and Research Initiative — or ARMI — and the USGS Powell Center for Analysis and Synthesis. ARMI is a national program focusing on amphibian research to stop or reverse the worldwide decline in amphibian populations from habitat change to disease.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2016/01/160120142729.htm  Original web page at Science Daily

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Researchers identify areas of plague risk in western United States

Researchers at SUNY Downstate Medical Center have identified and mapped areas of high probability of plague bacteria in the western United States. Their findings were published in a recent edition of the journal PeerJ.

This investigation predicted animal plague occurrence across western states based on reported occurrences of plague in sylvan (wild) and domestic animal hosts. Plague is a disease caused by Yersinia pestis, a bacterium found in rodents and their fleas in many areas around the world.

“This study used surveillance data of plague in wild and domestic animals in the American West to identify and map those areas with the greatest potential for human exposure to this infection, which can be particularly deadly when transmitted to humans,” said Michael Walsh, PhD, MPH, assistant professor in the Department of Epidemiology and Biostatistics in the School of Public Health at SUNY Downstate.

“The findings can be used by public health agencies to target specific areas for enhanced plague surveillance within areas and counties predicted to be at high risk, as well as by other research teams to direct the sampling of local wildlife populations for the identification of Yersinia pestis in wild animals that find themselves in close proximity to humans and human developed landscapes,” he added.

According to the federal Centers for Disease Control and Prevention (CDC), plague was first introduced into the United States in 1900, by rat-infested steamships that had sailed from affected areas. Epidemics occurred in port cities, with the last urban plague epidemic in the United States occurring in Los Angeles from 1924 through 1925. Plague then spread from urban rats to rural rodent species, and became entrenched in many areas of the western United States. Since that time, plague has occurred as scattered cases in rural areas. Most human cases in the United States occur in two regions: Northern New Mexico, northern Arizona, and southern Colorado; and California, southern Oregon, and far western Nevada.

The CDC also notes that in recent decades, an average of seven human plague cases has been reported each year (range: 1-17 cases per year). Plague has occurred in people of all ages (infants up to age 96), though 50% of cases occur in people ages 12-45.

The authors note in their article that while zoonotic (animal) transmission to humans is much less common in modern times, significant plague risk remains in parts of the western U.S. Moreover, risk to some threatened species that are part of the epizootic cycle can be quite substantive.

This investigation attempted to predict the risk of plague across the western US by modeling the ecologic niche of plague in sylvan and domestic animals identified between 2000 and 2015. An algorithm was used to predict this niche based on climate, altitude, land cover, and the presence of an important enzootic (carrier) species, Peromyscus maniculatus (a rodent commonly known as the North American deermouse).

This model demonstrated good predictive ability and identified areas of high risk in central Colorado, north-central New Mexico, and southwestern and northeastern California.

The presence of P. maniculatus, altitude, precipitation during the driest and wettest quarters, and distance to artificial surfaces, all contributed substantively to maximizing the gain function. These findings add to the known landscape epidemiology and infection ecology of plague in the western U.S. and may suggest locations of particular risk to be targeted for wild and domestic animal intervention.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/12/151228174447.htm  Original web page at Science Daily

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Bacillus cereus is able to resist certain antibiotic therapies

The pathogenic bacterium Bacillus cereus causes vomiting and diarrhea as well as systemic and local infections. A team of researchers has reported for the first time that B. cereus, following contact with certain antibiotics, can switch into a special slowed-down mode. The bacteria then form small colony variants (SVCs) that are difficult to diagnose and almost impossible to treat with certain antibiotics. This discovered mechanism may provide an alternative explanation for antibiotic resistance.

The bacterium B. cereus had so far been considered to be exclusively endospore-forming. In response to harsh conditions, the bacteria form protective endospores enabling them to remain dormant for extended periods. When conditions are more favourable, the endospores reactivate to become fully functioning bacteria.

Elrike Frenzel, Markus Kranzler and Monika Ehling-Schulz of the Institute of Microbiology at the University of Veterinary Medicine Vienna have now shown for the first time that B. cereus has an alternative lifestyle in the form of so called small colony variants (SCVs). In B. cereus these SCVs form in response to exposure with aminoglycoside antibiotics. SCVs grow slower than the original form of B. cereus. They have an altered metabolism and are resistant to those antibiotics which triggered this state, namely aminoglycosides.

“The bacterium protects itself against the harmful effects of the antibiotics by forming these Small Colony Variants. But B. cereus is usually treated with exactly those antibiotics which induce the SCV state. If an antibiotic triggers the formation of SCVs, it also triggers resistance,” first author Frenzel explains.

The mechanism discovered by Frenzel, Kranzler and Ehling-Schulz is of enormous significance in clinical practice. Traditional diagnostic methods are based on the identification of metabolic features of B. cereus. These tests will not detect SCVs, however, as they have a slower, altered metabolism. This may result in incorrect antibiotic therapies or even failed diagnoses. Study author Frenzel sees molecular-based diagnostics as the only way to diagnose this form of B. cereus.

Treating B. cereus infections using only aminoglycoside antibiotics could bear the risk of a prolonged infection. SCVs grow more slowly, but they still produce toxins that are harmful to the body. “In this case, a combination therapy with other antibiotic groups is advisable,” Frenzel recommends.

One species of bacteria that has been known for years to be a multiresistant hospital pathogen and which poses a life-threatening risk for immunocompromised individuals in particular is Staphylococcus aureus. Those bacteria also form SCVs, but unlike B. cereus they are capable of reverting to its original state. For B. cereus, the adaptation to a small colony variant appears to be final. “We believe that the SCV formation in B. cereus functions differently than in S. aureus,” says study author Ehling-Schulz.

“The ability to form SCVs appears to be of environmental significance for the bacteria,” Frenzel believes. “This alternative lifestyle allows the bacteria to avoid threatening stress factors such as antibiotic exposure. B. cereus are soil-dwelling, and other microorganism in the soil produce antibiotics. Here, too, the formation of SCVs would be an advantage for the bacteria.”

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/12/151228124703.htm  Original web page at Science Daily

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Save the salamanders

Batrachochytrium salamandrivorans (Bsal) is an emerging fungal pathogen that has caused recent die-offs of salamanders in Europe. Laboratory experiments have shown that it can kill some North American species as well, confirming a serious threat to salamander populations on the continent.

A Pearl (a short essay) published on December 10th in PLOS Pathogens summarizes what is known about the threat posed by the pathogen, discusses current initiatives in the USA, Canada, and Mexico to mitigate the threat, and calls for the creation of a North American Bsal Strategic Plan.

“All evidence suggests that we are at a critical time of action to protect global amphibian biodiversity by swift policy actions to prevent the translocation of Bsal,” state corresponding author Matthew Gray from the University of Tennessee in Knoxville, USA, and colleagues from the USA, Mexico, Canada, and Europe.

As they discuss, North America is a global hotspot for salamander biodiversity, accounting for about 50% of species worldwide. In the continent’s forests, the biomass of salamanders can exceed the biomass of all other vertebrate species, and salamanders are key players in a variety of ecosystems.

The lesson from other recently introduced fungal plant and animal pathogens (including those causing white-nose syndrome in bats or chestnut blight), they say, is that “preventing introduction is the best way to protect populations, but, if introduction occurs, rapid response is essential.”

Bsal was likely introduced to Europe from Asia through the commercial amphibian trade. Salamanders represent 5.5% of the amphibians imported into the USA, and their estimated annual market value is less than a million US dollars.

The authors mention that one European country has responded to the Bsal threat with a total import ban for salamanders. They do not call for such a ban in North America, but the proposed plan includes “strategies to prevent or reduce the risk of Bsal entry into the United States, Canada, and Mexico.”

Overall, they state that “the response to the threat of Bsal behooves a cooperative effort across non-governmental organizations, government agencies, academic institutions, zoos, the pet industry, and concerned citizens to avoid the potential catastrophic effects of Bsal on North American salamanders” and propose concrete steps to be taken immediately.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/12/151210144532.htm  Original web page at Science Daily

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Devising an inexpensive, quick tuberculosis test for developing areas

Tuberculosis (TB) is a highly infectious disease and a major global health problem, especially in countries with developing health care systems. Because there is no fast, easy way to detect TB, the deadly infection can spread quickly through communities. Now, a team reports in ACS Sensors the development of a rapid, sensitive and low-cost method for detecting the disease in resource-limited areas.

The typical way that physicians screen for TB, which is caused by the bacterium Mycobacterium tuberculosis (Mtb), is with a tuberculin skin test or an examination of a patient’s sputum under a microscope. To weed out false positives, a more reliable test that involves growing Mtb cultures can be performed, but that requires weeks to complete. For all of these methods, experienced personnel are needed. Another approach that is both quick and accurate is a nucleic acid amplification test, which makes many copies of the Mtb DNA in a sample. However, it is expensive and requires a lab setting. So, Matt Trau, Nicholas P. West and colleagues set out to create a simple, inexpensive and reliable way to quickly test for TB.

The researchers began with a newly created nucleic acid amplification test that does not require expensive lab equipment to detect Mtb. Still, this modified test typically uses costly fluorescence technology to read the results. So the team substituted the fluorescence detector with a colorimetric assay that changes to a blue hue if the infection is present, allowing health care workers to identify positive test results right away with the naked eye. They demonstrated how the modified diagnostic could be put on cheap, disposable electrochemical sensors for increased sensitivity, even in the field. Because the assay is inexpensive, quick and highly specific for the Mtb bacterium, the researchers say it could have a big impact in low-resource communities.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/12/151216135828.htm  Original web page at Science Daily

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Wild toads saved from killer fungal disease

After a six-year effort, biologists say they have for the first time managed to rid a wild toad species of a lethal fungal disease that threatens amphibians around the world.

Midwife toads on the Spanish island of Mallorca are now free of the chytrid fungus Batrachochytrium dendrobatidis, says Jaime Bosch, an evolutionary biologist at Spain’s National Museum of Natural History in Madrid. His team reported their success in the journal Biology Letters on 18 November. But the successful treatment — which involved treating tadpoles with an antifungal drug and chemically cleansing their ponds — may not be widely applicable to the habitats of other amphibian species that are threatened by chytrid, the researchers and others say.

The fungal disease is one of the greatest threats amphibians face across the globe: chytrid has already wiped out hundreds of species of frogs. Bosch and his colleagues in Spain and the United Kingdom first set out to save isolated populations of vulnerable midwife toads on Mallorca in 2009. The fungus was spreading on the toads’ skin, stifling their ability to breathe and manage their water balance, and ultimately killing them.

The researchers removed all the toads’ tadpoles and treated them in the laboratory with the antifungal drug itraconazole, while also draining and drying out their ponds in the hope of eliminating the pathogen. But after they were returned home – via helicopter – the first batch of successfully treated tadpoles was soon infected with the fungus again.

In 2012, the researchers tried again: this time, they drained and treated one set of ponds with Virkon S, an agricultural disinfectant made by DuPont. Tadpoles that were returned to those ponds a year later remained healthy, whereas those returned to ponds that were drained but not treated fell ill. After disinfecting the rest of the ponds, the researchers found no evidence of fungal infection two years on.

It is still unclear exactly where and how the fungus lingered in the untreated drained ponds, though Bosch and his team suspect that tadpoles were being reinfected by adult toads that remained tucked out of sight. The team sprayed disinfectant into nooks and crannies, so may have managed to reach the hidden adults.

“It’s pretty exciting that they were able to eliminate chytrid fungus in multiple sites across the island,” says Karen Lips, a conservation biologist at the University of Maryland, College Park. But Lips thinks that the treatment may only work in specific habitats. Mallorca is dry, with granite-carved ponds that flood seasonally, and few other species live there that could reintroduce the fungus. “Not many other places are geared to this approach,” Lips says. Exceptions include other isolated environments such as captive breeding programmes, zoos, laboratories and other kinds of islands — for example, urban islands and mountaintops. Still, she says, in places where species are endangered and costs are not a barrier, “I think this shows there are certain things you can do.”

To rid many amphibians of their fungal infection, it will be necessary to find another way, Bosch agrees. But the study shows that it may be worth trying the aggressive chemical intervention in some circumstances, he says. One of Bosch’s co-authors, Trent Garner of the Zoological Society of London, would like to see more mitigation efforts. “We spray for fungal infections in our crops every year,” he says. “Are there other things that we could use that could be applied environmentally and at a large scale?”

Doug Woodhams, an amphibian disease ecologist at the University of Massachusetts, Boston, hopes that interventions that don’t involve extensive spraying of antifungal chemicals might also work. In his laboratory he is trying probiotic therapy, which introduces beneficial microbes to fight fungal infection — but he has yet to prove that it works in the wild.

Meanwhile, in southeast continental Spain, which has a similar geographical landscape to Mallorca, Bosch and his colleagues are using their method to try to protect populations of the Betic midwife toad. Endemic to the region for millions of years, the toads now inhabit a landscape where humans have shifted water into artificial ponds meant for cattle. The toads now make these plastic-lined pools their home — a perfect setting in which to knock out the chytrid fungus.

Artificial cattle ponds in southeast Spain, where fungal-infected Betic midwife toads now reside, will also be cleansed.

Nature doi:10.1038/nature.2015.18814

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/wild-toads-saved-from-killer-fungal-disease-1.18814  Original web page at Nature

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Preventing dental implant infections

One million dental implants are inserted every year in Germany, and often they need to be replaced due to issues such as tissue infections caused by bacteria. In the future, these infections will be prevented thanks to a new plasma implant coating that kills pathogens using silver ions.

Bacterial infection of a dental implant is a dreaded complication, as it carries with it a high risk of jawbone degeneration. Implanting an artificial dental root sets off a race between infectious pathogens and the body’s own cellular defenses. If the bacteria win, they form a biological film over the titanium to protect themselves from antibiotics. Once the implant is colonized by germs, the result is an inflammatory reaction, which can result in bone atrophy.

To lower the risk of infection and improve the long-term effectiveness of the implant, researchers at the Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Bremen have developed a new type of implant coating in cooperation with industry partners. The DentaPlas coating helps prevent the growth of bacteria, thus allowing the implant to properly take hold and thereby form a faster and more permanent bond with the jawbone. The trick to this lies in combining surface materials that feature physical as well as chemical properties. “We have given the DentaPlas coating a rough texture, which promotes cellular growth, in addition to combining it with a hydrophilic plasma polymer coating, which attracts moisture,” says Dr. Ingo Grunwald, project manager at the IFAM. Researchers have integrated silver nanoparticles into the thin plasma polymer coating, which is up to just 100 nanometers thick. The silver nanoparticles dissolve over a period of several weeks, and during that time they continuously release small quantities of anti-microbial silver ions, which kill bacteria.

“The DentaPlas system consists of three layers, with two plasma polymer layers surrounding a center layer of silver. Within this structure a biocide reservoir is formed, and the outermost layer releases the ions. This is beneficial because it prevents direct contact between the tissue and the silver particles, which can be toxic when exposed,” says developer Dr. Dirk Salz. Researchers can tailor the silver concentration as well as the thickness of the layers and their porosity. This allows the silver ions to penetrate the outermost plasma polymer layer over a set period of time deemed necessary to properly integrate the implant. When the silver reservoir is exhausted, no more silver ions are released, thus avoiding any long-term toxic effects.

In trials using finished implants and titanium test samples, the IFAM researchers demonstrated that the DentaPlas coating is not only anti-microbial but also fully biocompatible and sterilizable. The test samples were coated using a plasma polymerization facility at the IFAM in Bremen. Researchers confirmed the mechanical stability and robustness of the DentaPlas coating in trials using the lower jawbones of pigs taken from butcher shops. Here, they subjected the DentaPlas coated implants to the rigors of being screwed into place using the instruments found in modern dental practices. The DentaPlas coating passed this stress test with flying colors. Project partner and Fraunhofer spinoff Bio Gate AG successfully transferred the processes of coating the test samples and titanium screws to its own production facilities. The medical technology company is also the manufacturer of the DentaPlas three-layer coating system.

A demonstration unit of the plasma polymer coating is currently available. Researchers will be presenting a dental implant featuring the DentaPlas coating at the MEDICA trade fair in Düsseldorf from November 16 -19 at the joint Fraunhofer booth.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/11/151104130046.htm  Original web page at Science Daily

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* Intensive farming link to bovine TB

Intensive farming practices such as larger herd size, maize growth, fewer hedgerows and the use of silage have been linked to higher risk of bovine TB, new research has concluded.

A study by the University of Exeter, funded by BBSRC and published in the Royal Society journal Biological Letters, analysed data from 503 farms which have suffered a TB breakdown alongside 808 control farms in areas of high TB risk.

Dr Fiona Mathews, Associate Professor in Mammalian Biology, who led the study, said: “TB is absolutely devastating for farming, and it’s essential that workable solutions are found. In the worst hit areas, farms are frequently affected over and over again with crippling consequences. If lower intensity production means better animal health, it offers a sustainable long-term strategy in high risk areas.”

The last few decades have seen radical changes in farming practices. Half of British dairy farmers have gone out of business since 2002. Those that remain have larger herds and greater productivity: average herd size increased from 75 animals in 1996 to 133 in 2014 (a rise of 77%), and the annual yield increased from 5,775 per cow in 1995 to 7,535l per cow in 2013 (a rise of 27%).

The team found that farms with herds of 150 cattle or more were 50% more likely to suffer a bovine TB outbreak than those with herds of 50 or fewer. Patterns of crop production and feeding were also important, with the risks increasing with practices linked with higher productivity systems. For every 10 hectares of maize — a favourite food of the badgers that play a role in transmitting the disease — bTB risk increased by 20%. The feeding of silage was linked with a doubling of the risk in both dairy and beef systems. Landscape features such as deciduous woodland, marshes and hedgerows were also important. For example, on farms with 50km of field boundaries, each extra 1km of hedgerow was linked with a 37% reduction in risk. This is likely to be because there is less contamination of pasture by badger faeces and urine in hedgerow-rich areas. Marshland was associated with increased risk, possibly as a secondary effect of infection with liver fluke — a disease linked with wet environments and which interferes with the diagnosis of bTB in cattle.

Dr Mathews said: “To beat TB, we need to ensure our approach is robust and evidence-based. This is the first large-scale study to link a range of landscape-scale habitat features and farming practices with bTB. All of the effects we have found are additive, so changing several linked aspects of the farming system could potentially make a big difference. Farmers are already aware that biosecurity in the farmyard can help reduce the risk of bTB in cattle. We have now shown that wider environmental management is also important. By finding out more about these links, we hope that we can help eradicate this terrible disease.”

The paper, ‘Environmental Risk Factors Association with Bovine Tuberculosis in Cattle high Risk Areas’, is published online in the journal Biological Letters today.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/11/151111055318.htm  Original web page at Science Daily

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Human handouts could be spreading disease from birds to people

People feeding white ibises at public parks are turning the normally independent birds into beggars, and now researchers at the University of Georgia say it might also be helping spread disease.

They recently launched a study to find out how being fed by humans is changing the health, ecology and behavior of white ibises in south Florida, where construction and land development is drying up their wetland habitats.

The birds normally feed on aquatic animals like fish, snails and crayfish, but they are now becoming accustomed to being fed items such as bread, fast food and popcorn by people at parks, said Sonia Hernandez, an associate professor with joint appointments in UGA’s Warnell School of Forestry and Natural Resources and College of Veterinary Medicine. This shift in feeding behavior could have serious consequences not just for the white ibises, she said, but also to people.

“In a previous study, and using molecular typing methods, we found that the strains of salmonella bacteria that white ibises are infected with are the same that some people get sick from, particularly in Florida,” Hernandez said. “Because white ibises move from urban to natural environments readily, they might be responsible for moving these strains around over large distances.”

Hernandez is working with other UGA researchers on the five-year, $2.1 million project, funded by the National Science Foundation’s Ecology and Evolution of Infectious Diseases Program. Their findings could apply to other wildlife species that have grown cozy with humans at public parks and other human-altered landscapes, she said.

Other researchers on the project are Jeff Hepinstall-Cymerman, an associate professor in the Warnell School; Sonia Altizer, a professor, and Richard Hall, an assistant research scientist, both in the Odum School of Ecology; and Kristen Navara, an associate professor in the College of Agricultural and Environmental Sciences.

The white ibis is most commonly found in Florida, although it can be spotted along the Atlantic coast as far north as North Carolina and on the Gulf Coast as far as Louisiana. They are normally nomadic, can travel for miles every day and typically spend much of their day searching for food.

But why expend energy searching for food when humans at public parks will give it to them, Altizer said. “If white ibises have a reliable food source, they might form larger flocks that stay put year-round near the parks.” This shift toward more sedentary behavior could allow pathogens transmitted through feces, like salmonella, to build up and pose risks for both birds and humans.

Greater numbers of ibises in urban parks also puts them contact with animals they wouldn’t normally meet in natural environments, like muscovy and mallard ducks, gulls and other common city birds — all reservoirs of diseases for birds.

As part of the project, the researchers will focus on white ibises in Palm Beach County, Florida, where Hernandez has been conducting field monitoring of the birds since 2010. The research site will span six urban and six natural areas in the county, and researchers will conduct field sampling of white ibises on a quarterly basis for two years to accurately estimate the birds’ population size.

They will put identification bands on the captured birds before releasing them, track movements using GPS devices, record basic data about each ibis marked, take blood samples and collect feces to determine salmonella infections.

Researchers are focusing on salmonella because it causes one of the most significant diarrheal diseases for people and can cause mortality in young wading birds.

“GPS technology is not just for humans anymore,” Hepinstall-Cymerman said. “We can now get up to 12 locations a day and for up to two years to understand how birds we capture at urban sites behave compared to birds caught at natural sites.”

If urban birds are roosting with birds that primarily use natural sites, diseases originating in urban areas could be spread throughout the white ibis population in Florida, he said. It doesn’t help that urbanized white ibises might also have weaker immune systems — most likely caused by contact with people, poor diets and stress from living in less-than-optimal environments.

“In fact, we are finding that urban ibises have extremely high levels of stress hormones and weak immune systems compared with other birds,” Navara said. “Ultimately, this could affect how pathogens, including salmonella, are being transmitted among individuals and between the birds and humans.”

Hall said it’s understandable that people would feed the friendly looking birds they see in parks — and it’s done with the best of intentions. However, researchers hope this project will raise awareness about how “helping” wildlife by feeding them can have unintended harmful effects.

“We also hope that these studies will inform good practices by which people can continue to enjoy encounters with wildlife in their backyards and cities, for example by developing good practices for bird feeder hygiene, what kinds of food to provide and knowing when to put up — and take down — feeders,” Hall said.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/11/151111172339.htm  Original web page at Science Daily

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* Staphylococcus aureus Achilles’ heel

Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking amongst the leading causes of skin and soft tissue infections, as well as severe pneumonia. Scientists attempt to work out new strategies to fight against this pathogen, of which numerous strains are now resistant to antibiotic treatments. One of the bacterium’s most impressive weapons is α-toxin, which provokes the destruction of human cells. An international project led by the Stanford University School of Medicine in California, in collaboration with the University of Geneva (UNIGE) in Switzerland, allowed to identify the components of our cells that modulate the virulence of this toxin, in particular the PLEKHA7 protein. By eliminating expression of the latter, cells gained the ability to recover from α-toxin injury, and mice lacking PLEKHA7 exhibited improved healing from bacterial skin infection as well as enhanced survival of pneumonia. The results, which pave the way to new potential therapies, are published in the journal PNAS.

The invasive power of Staphylococcus aureus is largely due to α-toxin, which destroys cells by piercing their membranes. The adherens junctions, which tie neighboring cells to one another and thus contribute to the formation of our tissues, were discovered to play an important role in the spreading of this infection. “Our results indicate that several components of the adherens junctions are involved in controlling the virulence of α-toxin, to varying degrees,” explains Lauren Popov, PhD student at Stanford’s School of Medicine and senior author of the study. The leading role is assumed by PLEKHA7, a protein discovered by the team of Sandra Citi, professor at the Department of Cell Biology of the Faculty of Science at UNIGE and co-director of the study.

To determine the importance of PLEKHA7 in modulating Staphylococcus aureus virulence, the biologists infected cells that do not express the gene coding for this protein. They observed that these cells gained the ability to recover from α-toxin injury. “Moreover, by infecting mice genetically deprived of PLEKHA7 with a multiresistant bacterial strain (MRSA), we observed improved healing from bacterial skin infection, as well as enhanced survival of pneumonia,” reveals Manuel Amieva, professor of microbiology and immunology and of pediatrics at Stanford’s School of Medicine and co-senior author of the study. The researchers are trying to understand how PLEKHA7 controls the action of α-toxin. One of their hypotheses is that this protein could aggravate bacterial toxicity by transmitting signals inducing cells’ self-destruction. “Since PLEKHA7 controls disease severity in both skin infection and lethal pneumonia, we suggest to target this non-essential component of the adherens junctions as a potential therapy to reduce the virulence of MRSA strains,” conclude the authors. Following the discovery of PLEKHA7’s importance during infections due to Staphylococcus aureus, several approaches are currently explored to find a way to inhibit this protein and limit bacterial spreading.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/10/151021083523.htm  Original we page at Science  Daily

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Novel theoretical approach to reduce antibiotic resistance

The combination and sequence of antibiotics can promote or hinder the development of antibiotic-resistant bacteria.

It is estimated that each year in the United States 2 million people become infected with bacteria that are resistant to one or more types of antibiotics, and at least 23,000 people will die because of these infections. This problem is being exacerbated by overuse of antibiotics for livestock and also in community clinical practice. This overuse, combined with the slow pace of novel drug discovery is a growing threat to public health. In response to this, Moffitt Cancer Center researchers have developed a novel mathematical method inspired by Darwinian evolution to use current antibiotics to eliminate or reduce the development of antibiotic-resistant bacteria.

According to the Centers for Disease Control, one of the core actions that can be taken to fight antibiotic-resistant infections is to improve the use of antibiotics that currently exist. One approach to achieve this is by using different combinations or sequences of antibiotics; however, given the high number of antibiotics in existence, it would be extremely difficult to experimentally identify the best combination or sequence of drugs

Moffitt researchers overcame this problem by developing a novel mathematical approach to analyze antibiotic resistance. They showed that the ability of the bacterium E. coli to survive in antibiotics could be either promoted or hindered depending on the sequence of antibiotics given. They discovered that approximately 70 percent of different sequences of 2 to 4 antibiotics lead to resistance to the final drug

“Our results suggest that, through careful ordering of antibiotics, we may be able to steer evolution to a dead end from which resistance cannot emerge,” said Daniel Nichol, lead author and graduate student jointly in the Oxford University Department of Computer Science and Moffitt’s Department of Integrated Mathematical Oncology.

“Our results can be easily tested in the laboratory, and if validated could be used in clinical trials immediately, as all of the compounds we studied are FDA approved and commonly prescribed,” said Jacob G. Scott, M.D., senior author and member of Moffitt’s Radiation Oncology and Integrated Mathematical Oncology Departments.

The researchers explained that their results also serve as a caution to healthcare workers, as the careless or random prescription of drugs that occurs could inadvertently lead to antibiotic resistance.

“While I’m an oncologist, the problem of the evolution of resistance to antibiotics is completely analogous to that of cancer’s evolution of resistance to targeted therapy, and the mathematical model we’ve used can be applied to both situations. Our next efforts are jointly focused on targeted therapy in lung cancer as well as on validating our existing results in bacteria,” said Scott.

http://www.sciencedaily.com/ Science Daily

http://www.sciencedaily.com/releases/2015/10/151009155413.htm  Original we page at Science Daily