Clostridioides difficile is a major cause of intestinal infection and diarrhea in individuals following antibiotic treatment. Exciting progress has been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defense against C. difficile infection. C. difficile-induced colitis is the most common and costly healthcare-associated infection with an estimate of nearly half a million cases in the U.S.A. and approximated 29,000 deaths occurring annually. Disease ranges from mild diarrhea to severe colitis. The intestinal microbiota provides resistance against C. difficile infection and disruption of the microbiota, for example through antibiotic treatment, allows the bacterium to proliferate in the gut. We investigate factors that regulate C. difficile virulence and host-microbiota mediated mechanisms that contribute to protection from disease, such as conversion of primary to secondary bile acids and activation of innate immune defenses.
C. difficile-specific publications
Keith JW, Dong Q, Sorbara MT, Becattini S, Sia JK, Gjonbalaj M, Seok R, Leiner IM, Littmann ER, Pamer EG. Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine. Immun. 2020 Mar 23;88(4):e00362-19. doi: 10.1128/IAI.00362-19. Print 2020 Mar 23.
Lewis BB, Carter RA, Ling L, Leiner I, Taur Y, Kamboj M, Dubberke ER, Xavier J, Pamer EG. Pathogenicity Locus, Core Genome, and Accessory Gene Contributions to Clostridium difficile Virulence. MBio. 2017; 8(4). pii: e00885-17.
Lewis BB, Carter RA, Pamer EG. Bile acid sensitivity and in vivo virulence of clinical Clostridium difficile isolates. Anaerobe. 2016; 41:32-36.
Abt MC, Lewis BB, Caballero S, Xiong H, Carter RA, Susac B, Ling L, Leiner I, Pamer EG. Innate Immune Defenses Mediated by Two ILC Subsets are Critical for Protection against Acute Clostridium difficile Infection. Cell Host & Microbe. 2015; 18(1):27-37.
Lewis BB, Buffie CG, Carter RA, Leiner I, Toussaint NC, Miller LC, Gobourne A, Ling L, Pamer EG. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection with Oral Vancomycin Compared with Metronidazole. Journal of Infectious Diseases. 2015; 212(10):1656-65.
Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littmann E, van den Brink MR, Jenq RR, Taur Y, Sander C, Cross J, Toussaint NC, Xavier JB, Pamer EG. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2014; 517:205-8.