The alternative sigma factor σB plays a crucial role in adaptive strategies of Clostridium difficile during gut infection

Environ Microbiol. 2017 May;19(5):1933-1958. doi: 10.1111/1462-2920.13696. Epub 2017 Mar 21.

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 σB in 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 σB controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σB does 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 σB also 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.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Clostridioides difficile / genetics*
  • Clostridioides difficile / pathogenicity
  • DNA Repair / genetics
  • Diarrhea / microbiology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Gastrointestinal Tract / microbiology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial / genetics*
  • Germ-Free Life
  • Mice
  • Mice, Inbred C3H
  • Oxidative Stress / genetics
  • Sigma Factor / genetics*
  • Sigma Factor / metabolism
  • Spores, Bacterial / genetics
  • Spores, Bacterial / growth & development
  • Up-Regulation
  • Virulence Factors / genetics

Substances

  • Bacterial Proteins
  • SigB protein, Bacteria
  • Sigma Factor
  • Virulence Factors