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The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization

Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) by Escherichia coli, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection of E. coli genomes from EnteroBase, enriched in clinical isolat...

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Autores principales: Tsoumtsa Meda, Landry L., Landraud, Luce, Petracchini, Serena, Descorps-Declere, Stéphane, Perthame, Emeline, Nahori, Marie-Anne, Ramirez Finn, Laura, Ingersoll, Molly A., Patiño-Navarrete, Rafael, Glaser, Philippe, Bonnet, Richard, Dussurget, Olivier, Denamur, Erick, Mettouchi, Amel, Lemichez, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519008/
https://www.ncbi.nlm.nih.gov/pubmed/36154446
http://dx.doi.org/10.1080/19490976.2022.2121577
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author Tsoumtsa Meda, Landry L.
Landraud, Luce
Petracchini, Serena
Descorps-Declere, Stéphane
Perthame, Emeline
Nahori, Marie-Anne
Ramirez Finn, Laura
Ingersoll, Molly A.
Patiño-Navarrete, Rafael
Glaser, Philippe
Bonnet, Richard
Dussurget, Olivier
Denamur, Erick
Mettouchi, Amel
Lemichez, Emmanuel
author_facet Tsoumtsa Meda, Landry L.
Landraud, Luce
Petracchini, Serena
Descorps-Declere, Stéphane
Perthame, Emeline
Nahori, Marie-Anne
Ramirez Finn, Laura
Ingersoll, Molly A.
Patiño-Navarrete, Rafael
Glaser, Philippe
Bonnet, Richard
Dussurget, Olivier
Denamur, Erick
Mettouchi, Amel
Lemichez, Emmanuel
author_sort Tsoumtsa Meda, Landry L.
collection PubMed
description Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) by Escherichia coli, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection of E. coli genomes from EnteroBase, enriched in clinical isolates of worldwide origins, suggest the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene, cnf1, is preferentially distributed in four common sequence types (ST) encompassing the pandemic E. coli MDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment, with known enhanced capacities to colonize the gastrointestinal tract. Statistical projections based on this dataset point to a global expansion of cnf1-positive multidrug-resistant ST131 strains from subclade H30Rx/C2, accounting for a rising prevalence of cnf1-positive strains in ST131. Despite the absence of phylogeographical signals, cnf1-positive isolates segregated into clusters in the ST131-H30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the same cnf1 allele. The suggested dominant expansion of cnf1-positive strains in ST131-H30Rx/C2 led us to uncover the competitive advantage conferred by cnf1 for gut colonization to the clinical strain EC131GY ST131-H30Rx/C2 versus cnf1-deleted isogenic strain. Complementation experiments showed that colon tissue invasion was compromised in the absence of deamidase activity on Rho GTPases by CNF1. Hence, gut colonization factor function of cnf1 was confirmed for another clinical strain ST131-H30Rx/C2. In addition, functional analysis of the cnf1-positive clinical strain EC131GY ST131-H30Rx/C2 and a cnf1-deleted isogenic strain showed no detectable impact of the CNF1 gene on bacterial fitness and inflammation during the acute phase of bladder monoinfection. Together these data argue for an absence of role of CNF1 in virulence during UTI, while enhancing gut colonization capacities of ST131-H30Rx/C2 and suggested expansion of cnf1-positive MDR isolates in subclade ST131-H30Rx/C2.
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spelling pubmed-95190082022-09-29 The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization Tsoumtsa Meda, Landry L. Landraud, Luce Petracchini, Serena Descorps-Declere, Stéphane Perthame, Emeline Nahori, Marie-Anne Ramirez Finn, Laura Ingersoll, Molly A. Patiño-Navarrete, Rafael Glaser, Philippe Bonnet, Richard Dussurget, Olivier Denamur, Erick Mettouchi, Amel Lemichez, Emmanuel Gut Microbes Research Paper Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) by Escherichia coli, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection of E. coli genomes from EnteroBase, enriched in clinical isolates of worldwide origins, suggest the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene, cnf1, is preferentially distributed in four common sequence types (ST) encompassing the pandemic E. coli MDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment, with known enhanced capacities to colonize the gastrointestinal tract. Statistical projections based on this dataset point to a global expansion of cnf1-positive multidrug-resistant ST131 strains from subclade H30Rx/C2, accounting for a rising prevalence of cnf1-positive strains in ST131. Despite the absence of phylogeographical signals, cnf1-positive isolates segregated into clusters in the ST131-H30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the same cnf1 allele. The suggested dominant expansion of cnf1-positive strains in ST131-H30Rx/C2 led us to uncover the competitive advantage conferred by cnf1 for gut colonization to the clinical strain EC131GY ST131-H30Rx/C2 versus cnf1-deleted isogenic strain. Complementation experiments showed that colon tissue invasion was compromised in the absence of deamidase activity on Rho GTPases by CNF1. Hence, gut colonization factor function of cnf1 was confirmed for another clinical strain ST131-H30Rx/C2. In addition, functional analysis of the cnf1-positive clinical strain EC131GY ST131-H30Rx/C2 and a cnf1-deleted isogenic strain showed no detectable impact of the CNF1 gene on bacterial fitness and inflammation during the acute phase of bladder monoinfection. Together these data argue for an absence of role of CNF1 in virulence during UTI, while enhancing gut colonization capacities of ST131-H30Rx/C2 and suggested expansion of cnf1-positive MDR isolates in subclade ST131-H30Rx/C2. Taylor & Francis 2022-09-25 /pmc/articles/PMC9519008/ /pubmed/36154446 http://dx.doi.org/10.1080/19490976.2022.2121577 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Tsoumtsa Meda, Landry L.
Landraud, Luce
Petracchini, Serena
Descorps-Declere, Stéphane
Perthame, Emeline
Nahori, Marie-Anne
Ramirez Finn, Laura
Ingersoll, Molly A.
Patiño-Navarrete, Rafael
Glaser, Philippe
Bonnet, Richard
Dussurget, Olivier
Denamur, Erick
Mettouchi, Amel
Lemichez, Emmanuel
The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title_full The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title_fullStr The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title_full_unstemmed The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title_short The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
title_sort cnf1 gene is associated with an expanding escherichia coli st131 h30rx/c2 subclade and confers a competitive advantage for gut colonization
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519008/
https://www.ncbi.nlm.nih.gov/pubmed/36154446
http://dx.doi.org/10.1080/19490976.2022.2121577
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