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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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2121577 |
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| author | Landry L. Tsoumtsa Meda Luce Landraud Serena Petracchini Stéphane Descorps-Declere Emeline Perthame Marie-Anne Nahori Laura Ramirez Finn Molly A. Ingersoll Rafael Patiño-Navarrete Philippe Glaser Richard Bonnet Olivier Dussurget Erick Denamur Amel Mettouchi Emmanuel Lemichez |
| author_facet | Landry L. Tsoumtsa Meda Luce Landraud Serena Petracchini Stéphane Descorps-Declere Emeline Perthame Marie-Anne Nahori Laura Ramirez Finn Molly A. Ingersoll Rafael Patiño-Navarrete Philippe Glaser Richard Bonnet Olivier Dussurget Erick Denamur Amel Mettouchi Emmanuel Lemichez |
| author_sort | Landry L. Tsoumtsa Meda |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-de7d105993ef4283a86dca81d2d69b67 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
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| series | Gut Microbes |
| spelling | doaj-art-de7d105993ef4283a86dca81d2d69b672025-08-20T02:29:58ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2121577The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonizationLandry L. Tsoumtsa Meda0Luce Landraud1Serena Petracchini2Stéphane Descorps-Declere3Emeline Perthame4Marie-Anne Nahori5Laura Ramirez Finn6Molly A. Ingersoll7Rafael Patiño-Navarrete8Philippe Glaser9Richard Bonnet10Olivier Dussurget11Erick Denamur12Amel Mettouchi13Emmanuel Lemichez14Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceUniversité Paris Cité et Université Sorbonne Paris Nord, INSERM U1137, IAME, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceInstitut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceInstitut Pasteur, Department of Immunology, Mucosal Inflammation and Immunity group, Paris, FranceInstitut Pasteur, Department of Immunology, Mucosal Inflammation and Immunity group, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Unité Ecologie et Evolution de la Résistance aux Antibiotiques, Département de Microbiologie, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Unité Ecologie et Evolution de la Résistance aux Antibiotiques, Département de Microbiologie, Paris, FranceUMR INSERM U1071, INRA USC-2018, Université Clermont Auvergne, Clermont-Ferrand, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Unité de Recherche Yersinia, Département de Microbiologie, Paris, FranceUniversité Paris Cité et Université Sorbonne Paris Nord, INSERM U1137, IAME, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceInstitut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, FranceEpidemiological 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2121577Escherichia coliExPECST131CNF1rho GTPasesgastrointestinal tract |
| spellingShingle | Landry L. Tsoumtsa Meda Luce Landraud Serena Petracchini Stéphane Descorps-Declere Emeline Perthame Marie-Anne Nahori Laura Ramirez Finn Molly A. Ingersoll Rafael Patiño-Navarrete Philippe Glaser Richard Bonnet Olivier Dussurget Erick Denamur Amel Mettouchi Emmanuel Lemichez The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization Gut Microbes Escherichia coli ExPEC ST131 CNF1 rho GTPases gastrointestinal tract |
| 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 | Escherichia coli ExPEC ST131 CNF1 rho GTPases gastrointestinal tract |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2121577 |
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