The Clostridium difficile spo0A Gene Is a Persistence and Transmission Factor

Clostridium difficile is a major cause of chronic antibiotic-associated diarrhea and a significant health care-associated pathogen that forms highly resistant and infectious spores. Spo0A is a highly conserved transcriptional regulator that plays a key role in initiating sporulation in Bacillus and Clostridium species. Here, we use a murine model to study the role of the C. difficile spo0A gene during infection and transmission. We demonstrate that C. difficile spo0Amutant derivatives can cause intestinal disease but are unable to persist within and effectively transmit between mice. Thus, the C. difficile Spo0A protein plays a key role in persistent infection, including recurrence and host-to-host transmission in mice. Clostridium difficile is a Gram-positive, sporogenic, anaerobicbacterium that is the most common cause of antibiotic-asso-ciated diarrhea within health care systems of the developed world (24, 34). Perturbation of the hosts ’ indigenous microbiota by broad-spectrum antibiotic treatment, such as clindamycin, is a major risk factor for C. difficile colonization, disease, and trans-mission (4, 10). C. difficile colonization is associated with a spec-trum of outcomes ranging from asymptomatic carriage, chronic diarrhea, and pseudomembranous colitis to multiple-organ dys-function syndrome (6, 17). The first-line antibiotic treatment fo