Standard therapy with oral antibiotics may disrupt the healthy gut microbiome, providing an opportunity for pathogens like the bacterium Clostridioides difficile (usually referred to as C. diff) to flourish in the gut and release toxins that damage and kill colon cells. Those toxins can cause severe diarrhea and colitis, leading to about 500,000 clinical infections, 30,000 colon resections and 15,000 deaths each year in the United States, mainly among hospitalized patients.
In a paper published November 1 in Nature Communications, Vern L. Schramm, Ph.D., and colleagues report developing two compounds, known as transition-state analogues, that neutralize the toxins responsible for the colon damage caused by C. diff. The toxins do their damage by releasing an enzyme that inactivates a family of proteins in cells lining the colon. In experiments involving mammalian cells, the Schramm lab’s compounds powerfully and specifically inhibit the enzyme released by the toxins, thereby preventing the toxins from causing damage. By neutralizing C. diff’s toxins rather than attacking C. diff bacteria themselves, the new compounds can prevent toxin-induced tissue damage without pressuring C. diff to develop resistance, as often occurs with standard antibiotics. Using standard antibiotics to attack C. diff bacteria can also kill other microbes, complicating the return to a healthy gut microbiome.
Dr. Schramm is professor and Ruth Merns Chair in Biochemistry. Ashleigh Paparella, Ph.D., the paper’s first author, is a postdoctoral research fellow in the Schramm lab.
Albert Einstein College of Medicine has filed patent application related to this research and is seeking licensing partners able to further develop and commercialize this technology. Interested parties can contact the Office of Biotechnology and Business Development at firstname.lastname@example.org
Posted on: Friday, December 03, 2021