Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections

Autor: Marie Claire Hipeaux, Olivier Clermont, Maxime Levert, Catherine Branger, Bertrand Picard, Claude Saint-Ruf, Michel Zivy, Susanna Nilsson, Françoise Norel, Thomas Ferenci, Sylvain Lespinats, Ivana Gudelj, Oana Zamfir, Béatrice Chane-Woon-Ming, Odile Bouvet, Katherine Phan, Olivier Tenaillon, Thierry Balliau, Stephane Cruvellier, Hervé Le Nagard, Erick Denamur
Přispěvatelé: Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Mathematics [Imperial College London], Imperial College London, School of Molecular Bioscience, The University of Sydney, 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., Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Hopital Louis Mourier - AP-HP [Colombes], Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Martin, Marie
Jazyk: angličtina
Rok vydání: 2010
Předmět:
MESH: Anti-Bacterial Agents/pharmacology
MESH: Sigma Factor/genetics
MESH: Genome
Bacterial
Genome
Polymerase Chain Reaction
MESH: Drug Resistance
Bacterial/genetics
MESH: Genotype
Mice
Cell Movement
MESH: Sigma Factor/metabolism
Genotype
Electrophoresis
Gel
Two-Dimensional
MESH: Animals
MESH: Genetic Variation
Biology (General)
MESH: Models
Theoretical
MESH: Cell Movement
Escherichia coli Infections
Genetics
MESH: Oxidants/pharmacology
0303 health sciences
Experimental evolution
MESH: Microbial Sensitivity Tests
MESH: Escherichia coli/pathogenicity
Microbiology/Microbial Evolution and Genomics
Virulence
MESH: Immunoblotting
Escherichia coli Proteins
Oxidants
Biological Evolution
3. Good health
Anti-Bacterial Agents
MESH: Escherichia coli Infections/microbiology
Female
MESH: Bacterial Proteins/metabolism
Research Article
Adult
DNA
Bacterial
Virulence Factors
QH301-705.5
Immunology
Immunoblotting
Sigma Factor
MESH: Escherichia coli/genetics
MESH: Biological Evolution
Microbial Sensitivity Tests
Biology
MESH: Bacterial Proteins/genetics
Microbiology
03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
MESH: Escherichia coli Proteins/genetics
MESH: Escherichia coli Infections/genetics
Virology
Genetic variation
Drug Resistance
Bacterial
Escherichia coli
MESH: Mutation/genetics
MESH: Virulence Factors/genetics
Animals
Humans
MESH: Escherichia coli/classification
MESH: Virulence/genetics
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Hydrogen Peroxide/pharmacology
Genetic diversity
MESH: Humans
030306 microbiology
Microbiology/Medical Microbiology
Genetic Variation
MESH: Adult
MESH: Polymerase Chain Reaction
Hydrogen Peroxide
Models
Theoretical
RC581-607
MESH: Electrophoresis
Gel
Two-Dimensional
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
MESH: Escherichia coli Infections/epidemiology
MESH: DNA
Bacterial/genetics
MESH: Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Mutation
Parasitology
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Immunologic diseases. Allergy
rpoS
MESH: Female
Genome
Bacterial
Zdroj: PLoS Pathogens, Vol 6, Iss 9, p e1001125 (2010)
PLoS Pathogens
PLoS Pathogens, Public Library of Science, 2010, 6 (9), pp.e1001125. ⟨10.1371/journal.ppat.1001125⟩
PLoS Pathogens, 2010, 6 (9), pp.e1001125. ⟨10.1371/journal.ppat.1001125⟩
ISSN: 1553-7374
1553-7366
DOI: 10.1371/journal.ppat.1001125⟩
Popis: 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.
Author Summary We investigated whether an infection is a site of pathogen within-species diversity. Our results indicate that there is indeed extensive diversity during human extraintestinal infections by Escherichia coli. This diversity was of two types, not mutually exclusive, as we found that patients were infected either by several distinct E. coli clones or by members of a single clone that exhibit micro-heterogeneity. The high degree of phenotypic diversity, including antibiotic resistance, suggests that there is no uniform selection pressure leading to a single fitter clone during an infection. We discuss a possible mechanism and a mathematical model that explains these unexpected results. Our data suggest that the evolution of diversity in the course of an infection and in in vitro experimental evolution in the absence of host immune selective pressure may have many parallels. 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.
Databáze: OpenAIRE
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