The cnf1 gene is associated with an expanding Escherichia coli ST131 H 30Rx/C2 subclade and confers a competitive advantage for gut colonization.

Autor:	Tsoumtsa Meda LL; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France., Landraud L; Université Paris Cité et Université Sorbonne Paris Nord, INSERM U1137, IAME, Paris, France.; Laboratoire Microbiologie-hygiène, AP-HP, Hôpital Louis Mourier, Colombes, France., Petracchini S; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France., Descorps-Declere S; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France.; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France., Perthame E; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France., Nahori MA; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France., Ramirez Finn L; Institut Pasteur, Department of Immunology, Mucosal Inflammation and Immunity group, Paris, France.; Université Paris Cité, Institut Cochin, CNRS UMR8104, INSERM U1016, Paris, France., Ingersoll MA; Institut Pasteur, Department of Immunology, Mucosal Inflammation and Immunity group, Paris, France.; Université Paris Cité, Institut Cochin, CNRS UMR8104, INSERM U1016, Paris, France., Patiño-Navarrete R; Institut Pasteur, Université Paris Cité, CNRS UMR6047, Unité Ecologie et Evolution de la Résistance aux Antibiotiques, Département de Microbiologie, Paris, France., Glaser P; Institut Pasteur, Université Paris Cité, CNRS UMR6047, Unité Ecologie et Evolution de la Résistance aux Antibiotiques, Département de Microbiologie, Paris, France., Bonnet R; UMR INSERM U1071, INRA USC-2018, Université Clermont Auvergne, Clermont-Ferrand, France.; Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire, Clermont-Ferrand, France., Dussurget O; Institut Pasteur, Université Paris Cité, CNRS UMR6047, Unité de Recherche Yersinia, Département de Microbiologie, Paris, France., Denamur E; Université Paris Cité et Université Sorbonne Paris Nord, INSERM U1137, IAME, Paris, France.; AP-HP, Laboratoire de Génétique Moléculaire, Hôpital Bichat, Paris, France., Mettouchi A; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France., Lemichez E; Institut Pasteur, Université Paris Cité, CNRS UMR6047, INSERM U1306, Unité des Toxines Bactériennes, Département de Microbiologie, Paris, France.
Jazyk:	angličtina
Zdroj:	Gut microbes [Gut Microbes] 2022 Jan-Dec; Vol. 14 (1), pp. 2121577.
DOI:	10.1080/19490976.2022.2121577
Abstrakt:	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 H 30Rx/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- H 30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the same cnf1 allele. The suggested dominant expansion of cnf1 -positive strains in ST131- H 30Rx/C2 led us to uncover the competitive advantage conferred by cnf1 for gut colonization to the clinical strain EC131GY ST131- H 30Rx/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- H 30Rx/C2. In addition, functional analysis of the cnf1 -positive clinical strain EC131GY ST131- H 30Rx/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- H 30Rx/C2 and suggested expansion of cnf1 -positive MDR isolates in subclade ST131- H 30Rx/C2.
Databáze:	MEDLINE
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