Research Description

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.

1. Beebe, MA, Paredes-Sabja, D, Kociolek, LK, Rodríguez, C, Sorg, JA. Phenotypic analysis of various Clostridioides difficile ribotypes reveals consistency among core processes. bioRxiv. 2025; :. doi: 10.1101/2025.01.10.632434. PubMed PMID:39829883 PubMed Central PMC11741275.
2. Huang, X, Johnson, AE, Brehm, JN, Do, TVT, Auchtung, TA, McCullough, HC et al.. Clostridioides difficile colonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an in vitro model. mSphere. 2025; :e0104924. doi: 10.1128/msphere.01049-24. PubMed PMID:39817755 .
3. Paredes-Sabja, D, Pizarro-Guajardo, M, Sorg, JA. Editorial: Pathogenic clostridia. Anaerobe. 2024;90 :102911. doi: 10.1016/j.anaerobe.2024.102911. PubMed PMID:39284521 .
4. Osborne, MS, Brehm, JN, Olivença, C, Cochran, AM, Serrano, M, Henriques, AO et al.. The Impact of YabG Mutations on Clostridioides difficile Spore Germination and Processing of Spore Substrates. Mol Microbiol. 2024;122 (4):534-548. doi: 10.1111/mmi.15316. PubMed PMID:39258427 .
5. Nerber, HN, Baloh, M, Brehm, JN, Sorg, JA. The small acid-soluble proteins of Clostridioides difficile regulate sporulation in a SpoIVB2-dependent manner. PLoS Pathog. 2024;20 (8):e1012507. doi: 10.1371/journal.ppat.1012507. PubMed PMID:39213448 PubMed Central PMC11392383.
6. Huang, X, Johnson, AE, Brehm, JN, Thanh Do, TV, Auchtung, TA, McCullough, HC et al.. Clostridioides difficile colonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an in vitro model. bioRxiv. 2024; :. doi: 10.1101/2024.07.17.603937. PubMed PMID:39071387 PubMed Central PMC11275744.
7. Martins, D, Nerber, HN, Roughton, CG, Fasquelle, A, Barwinska-Sendra, A, Vollmer, D et al.. Cleavage of an engulfment peptidoglycan hydrolase by a sporulation signature protease in Clostridioides difficile. Mol Microbiol. 2024;122 (2):213-229. doi: 10.1111/mmi.15291. PubMed PMID:38922761 PubMed Central PMC11309906.
8. Osborne, MS, Brehm, JN, Olivença, C, Cochran, AM, Serrano, M, Henriques, AO et al.. The impact of YabG mutations on C. difficile spore germination and processing of spore substrates. bioRxiv. 2024; :. doi: 10.1101/2024.06.10.598338. PubMed PMID:38915615 PubMed Central PMC11195116.
9. Brehm, JN, Sorg, JA. Theophylline-based control of repA on a Clostridioides difficile plasmid for use in allelic exchange. Anaerobe. 2024;88 :102858. doi: 10.1016/j.anaerobe.2024.102858. PubMed PMID:38692475 .
10. Nerber, HN, Sorg, JA. The small acid-soluble proteins of spore-forming organisms: similarities and differences in function. Anaerobe. 2024;87 :102844. doi: 10.1016/j.anaerobe.2024.102844. PubMed PMID:38582142 .