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Author Notes:

Address correspondence to Shonna M. McBride, shonna.mcbride@emory.edu

We thank Charles Moran, Abraham Sonenshein, and members of the McBride laboratory for suggestions and discussions throughout the course of this work.

We thank Jeremy Boss for the use of the Bio-Rad CFX96 real-time PCR detection system and Joseph Sorg for primers used for construction of the codY complement.

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 grant T32 AI106699 to K.L.N. L.B. and N.D. were supported by R01GM042219.

The content of this article is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • BACILLUS-SUBTILIS CODY
  • VIRULENCE GENE-EXPRESSION
  • DIPEPTIDE PERMEASE OPERON
  • CHAIN AMINO-ACIDS
  • TOXIN PRODUCTION
  • GLOBAL REGULATOR
  • CONJUGATIVE TRANSPOSON
  • IN-VITRO
  • TRANSCRIPTIONAL REGULATION
  • NUTRITIONAL REPRESSION

CodY-Dependent Regulation of Sporulation in Clostridium difficile

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Journal Title:

Journal of Bacteriology

Volume:

Volume 198, Number 15

Publisher:

, Pages 2113-2130

Type of Work:

Article | Final Publisher PDF

Abstract:

Clostridium difficile must form a spore to survive outside the gastrointestinal tract. The factors that trigger sporulation in C. difficile remain poorly understood. Previous studies have suggested that a link exists between nutritional status and sporulation initiation in C. difficile. In this study, we investigated the impact of the global nutritional regulator CodY on sporulation in C. difficile strains from the historical 012 ribotype and the current epidemic 027 ribotype. Sporulation frequencies were increased in both backgrounds, demonstrating that CodY represses sporulation in C. difficile. The 027 codY mutant exhibited a greater increase in spore formation than the 012 codY mutant. To determine the role of CodY in the observed sporulation phenotypes, we examined several factors that are known to influence sporulation in C. difficile. Using transcriptional reporter fusions and quantitative reverse transcription-PCR (qRT-PCR) analysis, we found that two loci associated with the initiation of sporulation, opp and sinR, are regulated by CodY. The data demonstrate that CodY is a repressor of sporulation in C. difficile and that the impact of CodY on sporulation and expression of specific genes is significantly influenced by the strain background. These results suggest that the variability of CodY-dependent regulation is an important contributor to virulence and sporulation in current epidemic isolates. This report provides further evidence that nutritional state, virulence, and sporulation are linked in C. difficile.

Copyright information:

© 2016, American Society for Microbiology.

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