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.
Chandra, H, Sorg, JA, Hassett, DJ, Sun, X. Regulatory transcription factors of Clostridioides difficile pathogenesis with a focus on toxin regulation. Crit Rev Microbiol. 2022; :1-16. doi: 10.1080/1040841X.2022.2054307. PubMed PMID:35389761 .
Simeon, RA, Zeng, Y, Chonira, V, Aguirre, AM, Lasagna, M, Baloh, M et al.. Correction to: Protease-stable DARPins as promising oral therapeutics. Protein Eng Des Sel. 2022;35 :. doi: 10.1093/protein/gzac003. PubMed PMID:35368085 PubMed Central PMC9081868.
Simeon, RA, Zeng, Y, Chonira, V, Aguirre, AM, Lasagna, M, Baloh, M et al.. Protease-stable DARPins as promising oral therapeutics. Protein Eng Des Sel. 2021;34 :. doi: 10.1093/protein/gzab028. PubMed PMID:34882774 PubMed Central PMC8861517.
Aguirre, AM, Yalcinkaya, N, Wu, Q, Swennes, A, Tessier, ME, Roberts, P et al.. Bile acid-independent protection against Clostridioides difficile infection. PLoS Pathog. 2021;17 (10):e1010015. doi: 10.1371/journal.ppat.1010015. PubMed PMID:34665847 PubMed Central PMC8555850.
Nerber, HN, Sorg, JA. The small acid-soluble proteins of Clostridioides difficile are important for UV resistance and serve as a check point for sporulation. PLoS Pathog. 2021;17 (9):e1009516. doi: 10.1371/journal.ppat.1009516. PubMed PMID:34496003 PubMed Central PMC8452069.
Baloh, M, Sorg, JA. Clostridioides difficile SpoVAD and SpoVAE Interact and Are Required for Dipicolinic Acid Uptake into Spores. J Bacteriol. 2021;203 (21):e0039421. doi: 10.1128/JB.00394-21. PubMed PMID:34424035 PubMed Central PMC8508128.
McAllister, KN, Martinez Aguirre, A, Sorg, JA. The Selenophosphate Synthetase Gene, selD, Is Important for Clostridioides difficile Physiology. J Bacteriol. 2021;203 (12):e0000821. doi: 10.1128/JB.00008-21. PubMed PMID:33820795 PubMed Central PMC8315937.
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.