My lab is focused on the mechanisms of spore germination and bile acid resistance in Clostridium difficile. C. difficile is a Gram-positive, spore forming, anaerobe that causes infections in people who have undergone antibiotic regimens. Previously, we had shown that certain bile acids promote C. difficile spore germination while others inhibit germination. Bile acids are small molecules made by the liver that help the absorption of fat and cholesterol in the GI tract while also serving as a protective barrier against invading pathogens. Because C. difficile spores use the ratios of bile acids as cues for germination, the actively growing bacteria must have adapted means to avoid their toxic properties. We are currently focused on identifying these factors and the mechanisms by which C. difficile spores germinate.
Engevik, MA, Danhof, HA, Shrestha, R, Chang-Graham, AL, Hyser, JM, Haag, AM et al.. Reuterin disrupts Clostridioides difficile metabolism and pathogenicity through reactive oxygen species generation. Gut Microbes. 2020;12 (1):1788898. doi: 10.1080/19490976.2020.1795388. PubMed PMID:32804011 PubMed Central PMC7524292.
Shrestha, R, Cochran, AM, Sorg, JA. The requirement for co-germinants during Clostridium difficile spore germination is influenced by mutations in yabG and cspA. PLoS Pathog. 2019;15 (4):e1007681. doi: 10.1371/journal.ppat.1007681. PubMed PMID:30943268 PubMed Central PMC6464247.
Bouillaut, L, Dubois, T, Francis, MB, Daou, N, Monot, M, Sorg, JA et al.. Role of the global regulator Rex in control of NAD+ -regeneration in Clostridioides (Clostridium) difficile. Mol Microbiol. 2019;111 (6):1671-1688. doi: 10.1111/mmi.14245. PubMed PMID:30882947 PubMed Central PMC6561804.