A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination
Donnelly, M. Lauren; Li, William; Li, Yong-qing; Hinkel, Lauren; Setlow, Peter; Shen, Aimee
Clostridium difficile is a Gram-positive spore-forming obligate anaerobe that is a leading cause of antibiotic-associated diarrhea worldwide. In order for C. difficile to initiate infection, its aerotolerant spore form must germinate in the gut of mammalian hosts. While almost all spore-forming organisms use trans- membrane germinant receptors to trigger germination, C. difficile uses the pseu- doprotease CspC to sense bile salt germinants. CspC activates the related subtilisin-like protease CspB, which then proteolytically activates the cortex hy- drolase SleC. Activated SleC degrades the protective spore cortex layer, a step that is essential for germination to proceed. Since CspC incorporation into spores also depends on CspA, a related pseudoprotease domain, Csp family pro- teins play a critical role in germination. However, how Csps are incorporated into spores remains unknown. In this study, we demonstrate that incorporation of the CspC, CspB, and CspA germination regulators into spores depends on CD0311 (renamed GerG), a previously uncharacterized hypothetical protein. The reduced levels of Csps in gerG spores correlate with reduced responsiveness to bile salt germinants and increased germination heterogeneity in single-spore germination assays. Interestingly, asparagine-rich repeat sequences in GerG’s central region facilitate spontaneous gel formation in vitro even though they are dispensable for GerG-mediated control of germination. Since GerG is found exclusively in C. difficile, our results suggest that exploiting GerG function could represent a promising avenue for developing C. difficile-specific anti-infective therapies.
Donnelly, M. Lauren, & Li, William, & Li, Yong-qing, & Hinkel, Lauren, & Setlow, Peter, & Shen, Aimee. (January 2017). A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination. mBio, (8:1), p.. Retrieved from http://hdl.handle.net/10342/7949
Donnelly, M. Lauren, and Li, William, and Li, Yong-qing, and Hinkel, Lauren, and Setlow, Peter, and Shen, Aimee. "A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination". mBio. 8:1. (.), January 2017. April 21, 2021. http://hdl.handle.net/10342/7949.
Donnelly, M. Lauren and Li, William and Li, Yong-qing and Hinkel, Lauren and Setlow, Peter and Shen, Aimee, "A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination," mBio 8, no. 1 (January 2017), http://hdl.handle.net/10342/7949 (accessed April 21, 2021).
Donnelly, M. Lauren, Li, William, Li, Yong-qing, Hinkel, Lauren, Setlow, Peter, Shen, Aimee. A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination. mBio. January 2017; 8(1) . http://hdl.handle.net/10342/7949. Accessed April 21, 2021.