By sequencing the genomes of several strains of Klebsiella pneumoniae, scientists from the Institut Pasteur and the CNRS have revealed their genetic profile and pinpointed the genes responsible for their multiple antibiotic resistance and virulence. They have used these results to compile a database for the scientific community, providing high-resolution genetic fingerprints and information on genes of medical importance. This should make it easier to monitor Klebsiella pneumoniae outbreaks. The results of the study were published in the journal Emerging Infectious Diseases.
Paris, October 28, 2014
Klebsiella pneumoniae bacteria are resistant to multiple antibiotics – around 50% of strains are resistant to broad-spectrum cephalosporins, and in recent years strains have emerged that are resistant to the most powerful antibiotics, carbapenems. Some Klebsiella pneumoniae are responsible for hospital-acquired (nosocomial) infections of the respiratory and urinary tracts. Others cause invasive community-acquired infections, leading to liver abscesses, sepsis and severe pneumonia that can prove fatal.
The emergence of multiple antibiotic resistant bacteria is seriously limiting treatment options. Knowledge of the bacterial genome is therefore vital to improve efforts to control infections and respond to epidemic outbreaks.
Until now, only seven of the Klebsiella pneumoniae genes were being sequenced to create genetic fingerprints. The genetic variability of these sequences provided strain identity but results were hampered by limited resolution. Scientists from Sylvain Brisse's team (Evolutionary Microbial Genomics Unit, Institut Pasteur, CNRS, directed by Eduardo Rocha) used new high-throughput sequencing techniques to determine the full genomic sequence of strains and obtain a much more precise genetic fingerprint based on 700 genes. Around a hundred genes already known to be of medical importance – conferring either resistance or virulence – were also detected in the genomic sequences of Klebsiella pneumoniae. The scientists analyzed almost 200 strains obtained in collaboration with the Paris Public Hospital Network and other laboratories across the world.
The data generated enabled them to divide the various strains of Klebsiella pneumoniae into different clonal groups sharing the same resistance or virulence genes. This revealed that the bacteria found in hospitals carry multidrug resistant genes and only rarely contain the virulence genes associated with community-acquired infections, whereas community-acquired bacteria carry virulence genes but are generally susceptible to antibiotics. This data can be used to keep track of the emergence and development of epidemics, and in particular to monitor the worrying new phenomenon of antibiotic-resistant genes in bacteria that are already known to be responsible for severe community-acquired infections. It can also help in the interpretation of epidemics by enabling scientists to pinpoint grouped cases of patients infected by the same bacterial strain.
A unique bioinformatics platform has been set up to make this data available to the scientific community (scientists, microbiologists and hospital infection control teams): http://bigsdb.web.pasteur.fr/klebsiella/klebsiella.html. They can use this database to identify immediately which clonal group a given strain of K. pneumoniae belongs to from its genomic sequence, and to determine whether it carries one or more resistance or virulence genes.
The methodology used in this study could be applied to other bacteria, such as Listeria monocytogenes, which is responsible for foodborne infections that are often fatal for unborn babies.
Illustration: Disk diffusion antibiogram of a clinical strain of Klebsiella pneumoniae. In the culture of a bacterial strain, each disk is impregnated with a different antibiotic. The black circles around the disks indicate that the bacteria have been killed by the antibiotic and that they are therefore not resistant.
© Institut Pasteur/Simon Le Hello
This study was funded by the Greater Paris Authority and the IBEID LabEx Investing in the Future program.
Genomic Definition of Hypervirulent and Multidrug-Resistant Klebsiella pneumoniae Clonal Groups, Emerging Infectious Diseases, October 20, 2014
Suzanne Bialek-Davenet1,2,3,*, Alexis Criscuolo1,2,*, Florent Ailloud1, Virginie Passet1,2, Louis Jones1, Anne-Sophie Delannoy-Vieillard1, Benoit Garin4, Simon Le Hello1, Guillaume Arlet5,6,7, Marie-Hélène Nicolas-Chanoine3,6,8, Dominique Decré5,6,7, and Sylvain Brisse1,2
(1) Institut Pasteur, Paris, France
(2) Centre National de la Recherche Scientifique (CNRS), Paris
(3) Hôpital Beaujon, Clichy, France
(4) Institut Pasteur, Antananarivo, Madagascar
(5) Sorbonne Université, Paris
(6) Institut National de la Santé et de la Recherche Médicale (INSERM), Paris
(7) Hôpitaux de l’Est Parisien, Paris
(8) Faculté de Médecine, Université Paris Diderot, Paris
* These authors contributed equally to this study.