The flagellin FliC of Clostridium difficile is responsible for pleiotropic gene regulation during in vivo infection
| Autor: | Anne Collignon, Nigel P. Minton, Amira Barketi-Klai, Bruno Dupuy, Marc Monot, Sandra Hoys, Sylvie Lambert-Bordes, Imad Kansau, Sarah A. Kuehne |
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| Přispěvatelé: | Écosystème Microbien Digestif et Santé, Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Clostridia Research Group [Nottingham], University of Nottingham, UK (UON)- Centre for Biomolecular Sciences, School of Life Science [Nottingham], This study was supported by the European Union (HEALTH-F3-2008-223585)., European Project: 223585,EC:FP7:HEALTH,FP7-HEALTH-2007-B,HYPERDIFF(2008), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Bacterial Diseases Mutant lcsh:Medicine ATP-binding cassette transporter MESH: Virulence Mice Gene expression Medicine and Health Sciences Gastrointestinal Infections MESH: Animals lcsh:Science MESH: Bacterial Proteins Enterocolitis Pseudomembranous Genetics Regulation of gene expression MESH: Gene Expression Regulation Bacterial Multidisciplinary biology Virulence Genetic Pleiotropy Genomics Clostridium difficile 3. Good health Infectious Diseases Transcriptome Analysis Research Article Virulence Factors Clostridium Difficile MESH: Genetic Pleiotropy MESH: Enterocolitis Pseudomembranous Gastroenterology and Hepatology Microbiology Bacterial Proteins Animals Gene MESH: Mice MESH: Clostridium difficile MESH: Virulence Factors Bacteria Clostridioides difficile lcsh:R Gut Bacteria Organisms Biology and Life Sciences Computational Biology [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Gene Expression Regulation Bacterial Genome Analysis MESH: Male biology.protein bacteria lcsh:Q Genome Expression Analysis Flagellin MESH: Flagellin |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2014, 9 (5), pp.e96876. ⟨10.1371/journal.pone.0096876⟩ PLoS ONE, 2014, 9 (5), pp.e96876. ⟨10.1371/journal.pone.0096876⟩ PLoS ONE, Vol 9, Iss 5, p e96876 (2014) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0096876⟩ |
| Popis: | International audience; Clostridium difficile is the main agent responsible for hospital acquired antibiotic associated diarrhoea. In recent years, epidemic strains have emerged causing more severe infections. Whilst C. difficile has two major virulence factors, toxins TcdA and TcdB, it is generally accepted that other virulence components of the bacterium contribute to disease. Previously, it has been suggested that flagella expression from pathogenic bacteria might be implicated in virulence. In a recent study, we observed an increased mortality in a gnotobiotic mouse model when animals were colonized with an isogenic fliC mutant constructed in the PCR-ribotype 027 (B1/NAP1) strain R20291, while animals survived when colonized by the parental strain or after colonization by other high-toxin-producing C. difficile strains. To understand the reasons for this increased virulence, we compared the global gene expression profiles between the fliC-R20291 mutant and its parental strain using an in vitro and in vivo transcriptomic approach. The latter made use of the gnotobiotic mouse model. Interestingly, in the fliC mutant, we observed considerable up-regulation of genes involved in mobility, membrane transport systems (PTS, ABC transporters), carbon metabolism, known virulence factors and sporulation. A smaller but significant up-regulation of genes involved in cell growth, fermentation, metabolism, stress and antibiotic resistance was also apparent. All of these genes may be associated with the increased virulence of the fliC-R20921 mutant. We confirmed that the fliC mutation is solely responsible for the observed changes in gene expression in the mutant strain since expression profiles were restored to that of the wild-type strain in the fliC-complemented strain. Thus, the absence of FliC is directly or indirectly involved in the high mortality observed in the fliC mutant infected animals. Therefore, we provide the first evidence that when the major structural component of the flagellum is neutralized, deregulation of gene expression can occur during infection. |
| Databáze: | OpenAIRE |
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