title: The alternative sigma factor σBplays a crucial role in adaptive strategies of Clostridium difficile during gut infection.
abstract: Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σB. In this work, we studied the role of σBin the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σBcontrols the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σBdoes not control toxin gene expression. In agreement with the up-regulation of sporulation genes, the sporulation efficiency is higher in the sigB mutant than in the wild-type strain. sigB inactivation also led to increased sensitivity to acidification, cationic antimicrobial peptides, nitric oxide and ROS. In addition, we showed for the first time that σBalso plays a crucial role in oxygen tolerance in this strict anaerobe. Finally, we demonstrated that the fitness of colonisation by the sigB mutant is greatly affected in a dixenic mouse model of colonisation when compared to the wild-type strain.
authors.affiliation: Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kint
authors.affiliation: EA 4043, Unité Bactéries Pathogènes et Santé (UBaPS), Université Paris-Sud, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Janoir
authors.affiliation: Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Monot
authors.affiliation: EA 4043, Unité Bactéries Pathogènes et Santé (UBaPS), Université Paris-Sud, Université Paris-Saclay, 92290, Châtenay-Malabry, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoys
authors.affiliation: Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Soutourina
authors.affiliation: Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dupuy
authors.affiliation: Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martin-Verstraete
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D016360:Clostridioides difficile / Q000235:genetics* / Q000472:pathogenicity; D004260:DNA Repair / Q000235:genetics; D003967:Diarrhea / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D005856:Germ-Free Life; D051379:Mice; D008809:Mice, Inbred C3H; D018384:Oxidative Stress / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism; D013171:Spores, Bacterial / Q000235:genetics / Q000254:growth & development; D015854:Up-Regulation; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C079011:SigB protein, Bacteria; D012808:Sigma Factor; D037521:Virulence Factors