An Aniline-Substituted Bile Salt Analog Protects both Mice and Hamsters from Multiple Clostridioides difficile Strains
Jacqueline R. Phan, Dung M. Do, Minh Chau Truong, Connie Ngo, Julian H. Phan, Shiv K. Sharma, Angel Schilke, Chrisabelle C. Mefferd, Jacob V. Villarama, Dengxun Lai, Amber Consul, Brian P. Hedlund, Steven M. Firestine, Ernesto Abel-Santos
Abstract
germination inhibition activity against strain R20291, and the most active compounds were tested against other strains. An aniline-substituted bile salt analog, CaPA (cholic acid substituted with phenylamine), was found to be a better antigerminant than CamSA against eight different C. difficile strains. In addition, CaPA was capable of reducing, delaying, or preventing murine CDI signs with all strains tested. CaPA-treated mice showed no obvious toxicity and showed minor effects on their gut microbiome. CaPA's efficacy was further confirmed by its ability to prevent CDI in hamsters infected with strain 630. These data suggest that C. difficile spores respond to germination inhibitors in a strain-dependent manner. However, careful screening can identify antigerminants with broad CDI prophylaxis activity.