Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups

Multidrug-resistant and highly virulent Klebsiella pneumoniae isolates are emerging, but the clonal groups (CGs) corresponding to these high-risk strains have remained imprecisely defined. We aimed to identify K. pneumoniae CGs on the basis of genome-wide sequence variation and to provide a simple bioinformatics tool to extract virulence and resistance gene data from genomic data. We sequenced 48 K. pneumoniae isolates, mostly of serotypes K1 and K2, and compared the genomes with 119 publicly available genomes. A total of 694 highly conserved genes were included in a core-genome multilocus sequence typing scheme, and cluster analysis of the data enabled precise definition of globally distributed hypervirulent and multidrug-resistant CGs. In addition, we created a freely accessible database, BIGSdb-Kp, to enable rapid extraction of medically and epidemiologically relevant information from genomic sequences of K. pneumoniae. Although drug-resistant and virulent K. pneumoniae populations were largely nonoverlapping, isolates with combined virulence and resistance features were detected.

Klebsiella pneumoniae is a frequent cause of nosocomial infections and has also emerged as an agent of severe community-acquired infections, including pyogenic liver abscess, pneumonia, and meningitis. The rise of antimicrobial drug resistance in K. pneumoniae, a member of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) of bacterial pathogens, raises serious therapeutic challenges. Most multidrug-resistant (MDR) K. pneumoniae isolates, which produce extended-spectrum β-lactamases (ESBLs) and/or carbapenemases in combination with quinolone and aminoglycoside resistance, belong to particular clones. Invasive community-acquired isolates are predominantly of capsular serotypes K1 and K2 and appear to differ in clonal background from MDR isolates (7–11). Controlling the emergence of these 2 types of high-risk clones and mitigating the alarming prospect of strains that would combine high virulence with multidrug resistance requires a precise definition of clonal groups (CGs) and rapid identification of their medically relevant features. K. pneumoniae clones have been recognized so far by using multilocus sequence typing (MLST) based on 7 housekeeping genes. However, MLST fails to draw clear discontinuities between CGs. Rapid, high-throughput sequencing promises to revolutionize medical microbiology and molecular epidemiology by improving discriminatory power and providing access to the resistome and virulome of clinical isolates. However, it remains challenging to extract medically relevant information from genome sequences in a timely manner. The objectives of this work were to delineate precisely, based on genome-wide genotyping, CGs corresponding to highly virulent and MDR K. pneumoniae isolates; extract the antimicrobial drug resistance and virulence-associated genomic features of those CGs by using a rapid and simple bioinformatics tool; and detect potential dual-risk isolates carrying virulence and resistance genes.  Emerging Infectious Diseases  Original web page at Emerging Infectious Diseases