Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection

PLoS Pathog. 2013 May;9(5):e1003356. doi: 10.1371/journal.ppat.1003356. Epub 2013 May 9.

Abstract

Clostridium difficile spores must germinate in vivo to become actively growing bacteria in order to produce the toxins that are necessary for disease. C. difficile spores germinate in vitro in response to certain bile acids and glycine. In other sporulating bacteria, proteins embedded within the inner membrane of the spore sense the presence of germinants and trigger the release of Ca⁺⁺-dipicolinic acid (Ca⁺⁺-DPA) from the spore core and subsequent hydrolysis of the spore cortex, a specialized peptidoglycan. Based upon homology searches of known germinant receptors from other spore-forming bacteria, C. difficile likely uses unique mechanisms to recognize germinants. Here, we identify the germination-specific protease, CspC, as the C. difficile bile acid germinant receptor and show that bile acid-mediated germination is important for establishing C. difficile disease in the hamster model of infection. These results highlight the importance of bile acids in triggering in vivo germination and provide the first description of a C. difficile spore germinant receptor. Blocking the interaction of bile acids with the C. difficile spore may represent an attractive target for novel therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Bile Acids and Salts / metabolism*
  • Carrier Proteins / metabolism*
  • Clostridium Infections / metabolism*
  • Clostridium difficile / physiology*
  • Cricetinae
  • Female
  • Mesocricetus
  • Spores, Bacterial

Substances

  • Bacterial Proteins
  • Bile Acids and Salts
  • Carrier Proteins
  • CspC protein, Clostridium

Grant support

This work was supported by the American Heart Association National Scientist Development grant to JAS (No. 11SDG7160013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.