martes, 21 de octubre de 2014

Genomic Definition of Hypervirulent and Multidrug-Resistant Klebsiella pneumoniae Clonal Groups - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC


Genomic Definition of Hypervirulent and Multidrug-Resistant Klebsiella pneumoniae Clonal Groups - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 11—November 2014


Genomic Definition of Hypervirulent and Multidrug-Resistant Klebsiella pneumoniaeClonal Groups

Suzanne Bialek-Davenet1, Alexis Criscuolo1, Florent Ailloud, Virginie Passet, Louis Jones, Anne-Sophie Delannoy-Vieillard, Benoit Garin, Simon Le Hello, Guillaume Arlet, Marie-Hélène Nicolas-Chanoine, Dominique Decré, and Sylvain BrisseComments to Author 
Author affiliations: Institut Pasteur, Paris, France (S. Bialek-Davenet, A. Criscuolo, F. Ailloud, V. Passet, L. Jones, A.-S. Delannoy-Vieillard, S. Le Hello, S. Brisse)Centre National de la Recherche Scientifique (CNRS), Paris (S. Bialek-Davenet, A. Criscuolo, V. Passet, S. Brisse)Hôpital Beaujon, Clichy, France (S. Bialek-Davenet, M.-H. Nicolas-Chanoine)Institut Pasteur, Antananarivo, Madagascar (B. Garin)Sorbonne Université, Paris (G. Arlet, D. Decré)Institut National de la Santé et de la Recherche Médicale (INSERM), Paris (G. Arlet, M.-H. Nicolas-Chanoine, D. Decré)Hôpitaux de l’Est Parisien, Paris (G. Arlet, D. Decré)Faculté de Médecine, Université Paris Diderot, Paris (M.-H. Nicolas-Chanoine)


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. pneumoniaeisolates, 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 (1,2). The rise of antimicrobial drug resistance in K. pneumoniae, a member of the ESKAPE group (Enterococcus faeciumStaphylococcus aureusKlebsiella pneumoniaeAcinetobacter baumanniiPseudomonas aeruginosa, and Enterobacter species) of bacterial pathogens (3), 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 (46). Invasive community-acquired isolates are predominantly of capsular serotypes K1 and K2 and appear to differ in clonal background from MDR isolates (711). 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 (4,8,12). However, MLST fails to draw clear discontinuities between CGs (46). Rapid, high-throughput sequencing promises to revolutionize medical microbiology and molecular epidemiology (13,14) 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.

Dr Bialek-Davenet is a microbiologist working as a postdoctoral fellow in the Microbial Evolutionary Genomics Unit, Institut Pasteur. Her research interests include genomic epidemiology and resistance and virulence determinants of K. pneumoniae.


We are grateful to K. Jolley for advice on BIGSdb installation. We thank L. Lery and R. Tournebize for providing the complete genome sequence of strain CIP 52.145, J.-M. Thiberge for help in the initial setup of the BIGSdb-Kp database, and N. Nihotte for contributing to the Institut Pasteur BIGSdb home pages. The following colleagues are acknowledged for providing K. pneumoniae isolates or reference strains: B. De Barbeyrac (BD-DU), F. Randrianirina (BG94 and BG141), C. De Champs (CH137), E. Carbonelle (Zaire1), H. Courtade (100519185), E. van Duikeren (V9902406), C. Forestier (LM21 and CH1031), F. Jauréguy (BP1011625), P. A. D. Grimont (CDC 4241-71), A. Mérens (610356538), A. Merlet (20479), H.-L. Peng (CG43), D. Tainturier (MET1_63/88063), and J.-T. Wang (A3021 and A5011). We thank E. Rocha for helpful comments.
A.C. and genomic sequencing were supported financially by a grant from Region Île-de-France. S.B.-D. was supported by a postdoc grant from Assistance Publique–Hôpitaux de Paris and Institut Pasteur. This work was supported by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID).


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Suggested citation for this article: Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy-Vieillard AS, et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis. 2014 Nov [date cited]. eid2011.140206
DOI: 10.3201/eid2011.140206
1These first authors contributed equally to this article.

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