Identification of a Novel Lipoprotein Regulator of Clostridium difficile Spore Germination

• DOI: 10.1371/journal.ppat.1005239
• Publication Date: 2015-10-23T20:17:27Z
• Authors: Kelly A. Fimlaid; Owen Jensen; M. Lauren Donnelly; Michael B. Francis; Joseph A. Sorg; Aimee Shen
• Keywords: Spore germination

Clostridium difficile is a Gram-positive spore-forming pathogen and leading cause of nosocomial diarrhea. C. infections are transmitted when ingested spores germinate in the gastrointestinal tract transform into vegetative cells. Germination begins germinant receptor CspC detects bile salts gut. subtilisin-like serine pseudoprotease that activates related CspB protease through an unknown mechanism. Activated cleaves pro-SleC zymogen, which allows activated SleC cortex hydrolase to degrade protective layer. While these regulators essential for outgrow form toxin-secreting cells, mechanisms controlling their function have only been partially characterized. In this study, we identify lipoprotein GerS as novel regulator spore germination using targeted mutagenesis. A gerS mutant has severe defect fails even though it processes at wildtype levels. Using complementation analyses, demonstrate secretion, but not lipidation, necessary activate SleC. Importantly, loss attenuates virulence hamster model infection. Since appears be conserved exclusively Peptostreptococcaeace family members, our results contribute growing body work indicating evolved distinct exit from dormancy relative B. subtilis other organisms.