Journal Article

Molecular and Evolutionary Bases of Within-Patient Genotypic and Phenotypic Diversity in Escherichia coli Extraintestinal Infections

Phan, Katherine, Lespinats, Sylvain, Institut National de la Santé et de la Recherche Médicale (INSERM), Hipeaux, Marie Claire, Le Nagard, Hervé, Zivy, Michel, School of Molecular Bioscience ; The University of Sydney, MicroScope Platform, Picard, Bertrand, Hôpital Louis Mourier - AP-HP [Colombes] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saint-Ruf, Claude, M.L. was supported by a grant from the “Region Ile de France”, O.T. was funded by the “Agence Nationale de la Recherche” and E.D. was partially supported by the “Fondation pour la Recherche Médicale”. K.P. and T.F. were supported by the Australian Research Council, Bouvet, Odile, Gudelj, Ivana, Norel, Françoise, Denamur, Erick, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon) ; Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire ; Institut Pasteur [Paris] (IP)-Centre National de la Reche

2010

Overview

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies.

• Publisher: CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Animals / Anti-Bacterial Agents - pharmacology / Antibiotics / Bacteria / Bacterial genetics / Bacterial infections / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteriology / Biological Evolution / Cell Movement / Cloning / Colorectal diseases / DNA, Bacterial - genetics / Drug Resistance, Bacterial - genetics / E coli / Electrophoresis, Gel, Two-Dimensional / Escherichia coli / Escherichia coli - classification / Escherichia coli - genetics / Escherichia coli - pathogenicity / Escherichia coli Infections - epidemiology / Escherichia coli Infections - genetics / Escherichia coli Infections - microbiology / Escherichia coli Proteins - genetics / Evolution / Experiments / Female / Gastrointestinal diseases / Genetic aspects / Genetic Variation / Genome, Bacterial / Genotype / Health aspects / Humans / Hydrogen Peroxide - pharmacology / Immunoblotting / Infections / Life Sciences / Mathematical models / Mice / Microbial Sensitivity Tests / Microbiology / Microbiology and Parasitology / Microbiology/Medical Microbiology / Microbiology/Microbial Evolution and Genomics / Models, Theoretical / Molecular evolution / Molecular weight / Mutation / Mutation - genetics / Oxidants - pharmacology / Patients / Polymerase Chain Reaction / Sigma Factor - genetics / Sigma Factor - metabolism / Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Virulence - genetics / Virulence Factors - genetics