Inhibitors of Clostridium difficile spore germination and outgrowth
Inhibitors of Clostridium difficile spore germination
Tufts case T001523
• Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C. difficile-associated disease (CDAD). Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C. difficile spores has been studied in more detail and a particular secondary bile salt chenodeoxycholate has been demonstrated to inhibit the growth of C. difficile spores, thereby providing a novel potential therapy for CDAD. Several analogs of chenodeoxycholate have been tested that are even more effective inhibitors of C. difficile spore germination than chenodeoxycholate itself.
• The opportunity exists to establish a drug development program based on chenodeoxycholate analogs to develop novel and potent treatments for CDAD. Such drugs will have few, if any, side effects due to the unique target: inhibition of spore germination.
Why It Matters
• C. difficile is the most common causative agent of antibiotic-associated diarrhea and the primary cause of pseudomembranous colitis, a potentially fatal disease.
• The annual treatment-associated cost for C. difficile infection (CDI) in the United States is estimated to be between $750 million and $3.2 billion.3
• Despite available treatment for antibiotic-associated colitis and pseudomembranous colitis, relapses occur in 20-25% of patients. Vancomycin and metronidazole can be effective, but treated subjects are prone to relapse.
• Since relapses are so common, there is still a need for additional effective treatment and prevention of C. difficile-associated disease, particularly in humans.
US Patent 9,340,569, Issued May 17, 2016
• Abraham L. Sonenshein, Department of Molecular Biology, Tufts University School of Medicine
• J Bacteriol. April 2008 190: 2505-2512
• J. Bacteriol., Oct. 2009; 191: 1115-1117
• J. Bacteriol., Oct. 2010; 192: 4983–4990.