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Author Notes:

Shonna M. McBride: shonna.mcbride@emory.edu.

We give special thanks to Charles Moran, Linc Sonenshein, and members of the S. M. McBride lab for helpful suggestions and discussions during the course of this work, Aimee Shen for the spo0A plasmid, and Jeremy Boss for use of the Bio-Rad CFX96 real-time PCR detection system.

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.

Subjects:

Research Funding:

This research was supported by the U.S. National Institutes of Health through research grants DK087763, DK101870, and AI109526 to S.M.M. and training grant AI106699 to K.L.N. Microscopy studies were supported in part by the Emory University Integrated Cellular Imaging Microscopy Core.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Infectious Diseases
  • ANAEROBES GENUS CLOSTRIDIUM
  • PROTEIN ASPARTATE PHOSPHATASES
  • BACILLUS-SUBTILIS SPORULATION
  • TRANSPORT-SYSTEM
  • LACTOCOCCUS-LACTIS
  • CL.-SPOROGENES
  • GENETIC-CHARACTERIZATION
  • TRANSCRIPTIONAL CONTROL
  • SALMONELLA-TYPHIMURIUM
  • ENDOSPORE FORMATION

Journal Title:

Infection and Immunity

Volume:

Volume 82, Number 10

Publisher:

, Pages 4276-4291

Type of Work:

Article | Final Publisher PDF

Abstract:

The anaerobic gastrointestinal pathogen Clostridium difficile must form a metabolically dormant spore to survive in oxygenic environments and be transmitted from host to host. The regulatory factors by which C. difficile initiates and controls the early stages of sporulation in C. difficile are not highly conserved in other Clostridium or Bacillus species. Here, we investigated the role of two conserved oligopeptide permeases, Opp and App, in the regulation of sporulation in C. difficile. These permeases are known to positively affect sporulation in Bacillus species through the import of sporulation-specific quorum-sensing peptides. In contrast to other spore-forming bacteria, we discovered that inactivating these permeases in C. difficile resulted in the earlier expression of early sporulation genes and increased sporulation in vitro. Furthermore, disruption of opp and app resulted in greater virulence and increased the amounts of spores recovered from feces in the hamster model of C. difficile infection. Our data suggest that Opp and App indirectly inhibit sporulation, likely through the activities of the transcriptional regulator SinR and its inhibitor, SinI. Taken together, these results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in C. difficile than in Bacillus subtilis and suggest that nutrient availability plays a significant role in pathogenesis and sporulation in vivo. This study suggests a link between the nutritional status of the environment and sporulation initiation in C. difficile.

Copyright information:

© 2014, American Society for Microbiology.

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