Abstract
Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow these processes to be studied in detail. One such advance is the generation of a mouse-model of C. difficile infection. The development of this system is a major step forward in analyzing the genetic requirements for colonization and infection. While important, it is equally as important in understanding what differences exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination is an important step in C. difficile colonization. Mice produce several different bile acids that are not found in humans. These muricholic acids have the potential to impact C. difficile spore germination. Here we find that the three muricholic acids (α-muricholic acid, β-muricholic acid and ω-muricholic acid) inhibit C. difficile spore germination and can impact the growth of vegetative cells. These results highlight an important difference between humans and mice and may have an impact on C. difficile virulence in the mouse-model of C. difficile infection.
Highlights
Clostridium difficile is an anaerobic, spore-forming bacteria that is the leading cause of antibiotic-associated diarrhea
We find that all three muricholic acids can inhibit C. difficile spore germination with apparent affinities similar to what is observed for CDCA and that these compounds are growth inhibitory
The third muricholic acid, OMA (3a, 6a, 7b-trihydroxy-5b-cholanic acid) is produced by oxidation of the 6b-hydroxyl of b-muricholic acid followed by reduction of the compound to a 6a-hydroxyl group (Figure 1) by members of the mouse colonic microbiota [46,47]
Summary
Clostridium difficile is an anaerobic, spore-forming bacteria that is the leading cause of antibiotic-associated diarrhea. Antibiotic-treated hamsters are very sensitive to C. difficile infection with lethal disease presenting approximately 3 days after inoculation by C. difficile spores. While the hamster represents an excellent model of acute disease, hamsters typically succumb too quickly to disease to measure factors influencing colonization, representing only the full presentation of disease and not less severe symptoms when exposed to epidemic strains [12]. Such rapid progression of the disease and high mortality can pose problems when attempting to study relapsing infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
