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Author Notes:

Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, GA 30322. Phone: (404) 727-6192. Fax: (404) 727-8250. shonna.mcbride@emory.edu

We give special thanks to Dr. Charles Moran and members of the McBride lab for helpful suggestions and discussions during the course of this work and to Emily Weinert for advice on protein expression.

The authors declare no competing financial interests.

Subjects:

Research Funding:

This research was supported by the U.S. National Institutes of Health through research grants DK087763, DK101870, AI109526 and AI116933 to S.M.M and AI107029 to R.T.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Microbiology
  • PROTEIN ASPARTATE PHOSPHATASES
  • QUORUM-SENSING SYSTEM
  • BACILLUS-CEREUS GROUP
  • GENE-EXPRESSION
  • OLIGOPEPTIDE PERMEASE
  • COMPETENCE DEVELOPMENT
  • CONFORMATIONAL-CHANGES
  • ENTEROCOCCUS-FAECALIS
  • TRANSPORT-SYSTEM
  • SIGMA-FACTOR

A novel regulator controls Clostridium difficile sporulation, motility and toxin production

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Journal Title:

Molecular Microbiology

Volume:

Volume 100, Number 6

Publisher:

, Pages 954-971

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Clostridium difficile is an anaerobic pathogen that forms spores which promote survival in the environment and transmission to new hosts. The regulatory pathways by which C. difficile initiates spore formation are poorly understood. We identified two factors with limited similarity to the Rap sporulation proteins of other spore-forming bacteria. In this study, we show that disruption of the gene CD3668 reduces sporulation and increases toxin production and motility. This mutant was more virulent and exhibited increased toxin gene expression in the hamster model of infection. Based on these phenotypes, we have renamed this locus rstA, for regulator of sporulation and toxins. Our data demonstrate that RstA is a bifunctional protein that upregulates sporulation through an unidentified pathway and represses motility and toxin production by influencing sigD transcription. Conserved RstA orthologs are present in other pathogenic and industrial Clostridium species and may represent a key regulatory protein controlling clostridial sporulation.

Copyright information:

© 2016 John Wiley & Sons Ltd. This is the peer reviewed version of the following article, which has been published in final form. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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