Clostridioides difficile is the number one cause of hospital-acquired enteric infections in the USA. This anaerobic bacterium deploys two large protein exotoxins, TcdA and TcdB, that glucosylate and inactivate Rho-family GTPases. This process leads to cytoskeletal dysfunction, cell death, and inflammatory signaling, resulting in diarrhea and pseudomembranous colitis. In severe cases, it can cause toxic megacolon, bowel perforation, and death.

In addition to the acute phase of a C. difficile infection (CDI), about 30% of patients experience disease recurrence within 2 to 8 weeks following the initial episode. Furthermore, 25% of CDI patients may suffer from physiological bowel dysfunction, which can persist for years.

The Peritore Lab aims to uncover the mechanisms by which C. difficile toxins alter host epithelial physiology during both acute and chronic infections and to understand how these changes in the colonic environment affect the host, the pathogen, and the commensal microbiota. This is accomplished by employing both in vitro approaches, such as using recombinant protein toxins and human-derived organoids, and in vivo methods, including C. difficile mutants and mouse models of infection.

Current areas of interest are:
1) Toxin-mediated mechanisms of post-CDI bowel dysfunction.
2) The impact of TcdB sequence and structural variation on disease outcomes.
3) Multi-modal imaging to study C. difficile biofilms in situ.
4) The impacts of toxigenic C. difficile colonization in cystic fibrosis patients.

For more information, see: www.peritorelab.com