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New defense discovered against common hospital-acquired infection

Monday, August 22, 2020

Researcher of The Commonwealth Medical College co-authors study

Scranton, Pennsylvania – Researchers at The Commonwealth Medical College (TCMC) and the University of Texas Medical Branch at Galveston have discovered a molecular process by which the body can defend against the effects of Clostridium difficile infection (CDI), pointing the way to a promising new approach for treating an intestinal disease that has become more common, more severe, and harder to cure in recent years. As a result of their findings, published in the online August issue of the journal Nature Medicine, the researchers are preparing to launch clinical trials using their discovery as a new CDI therapeutic approach.

“We have discovered a key mechanism used by intestinal cells to defend themselves against Clostridium difficile infection (CDI), one of the most common hospital-acquired infections particularly in elderly patients,” stated Raj Kumar, PhD, co-author of the research paper, a basic scientist and professor of biochemistry at TCMC. Researchers have identified a new protective response called “nytrosylation” which can prevent toxins from attacking cells and causing an inflammatory response in the bowel. “In this study, we have identified structurally conserved nytrosylation motif, which can be utilized to produce a therapy to treat not only the effects of the CDI antibiotic-resistant bacteria but several other microbial infections,” Dr. Kumar continued. 

Identification of new treatment modalities to treat this infection would be a major advance. CDI is a bacterial infection that can cause diarrhea as well as more serious intestinal conditions such as colitis (inflammation of the colon); in the most severe cases CDI can be fatal. It is most commonly acquired in hospitals by patients – particularly the elderly – who are being treated with antibiotics for another infection. In the United States, several million people are infected each year, approximately double the incidence of a decade ago. The primary cause of the increase: the emergence of a new, highly virulent strain of the bacteria.

Currently, one of two potent antibiotics is used to treat the infection, but as many as 20 percent of patients experience a relapse and return of symptoms within a few weeks. “Our study suggests a novel therapeutic approach for treating Clostridium difficile infection by exploiting a newly discovered defense mechanism that has evolved in humans to inactivate microbial toxins,” said Tor C. Savidge, PhD, an associate professor in the Division of Gastroenterology and Hepatology at the University of Texas Medical Branch at Galveston and the paper’s lead author.

Clostridium difficile causes diarrhea and colitis by releasing two potent toxins into the gut lumen that bind to intestinal cells, initiating an inflammatory response that is associated with diarrhea. These toxins are released only when the bacteria are multiplying. When antibiotics are used to treat another infection it changes the bacterial landscape in the gut – and in the process, may kill bacteria that under normal conditions would compete with Clostridium difficile for energy. Scientists believe this may be what provides the opportunity for Clostridium difficile to grow and release its toxins.

Along with its potential to provide a much-needed new approach to treating CDI, the discovery could be applied to developing new treatments for other forms of diarrhea, as well as non-diarrheal diseases caused by bacteria.

Other study authors include: Charalabos Pothoulakis, M.D., Director of UCLA’s Inflammatory Bowel Disease Center from UCLA, Petri Urvil, Numan Oezguen, Ali Kausar, Aproteem Choudhury, Vinay Acharya, Irina Pinchuk, Alfredo G. Torres, Robert D. English, Michael Loeffelholz, and Werner Braun from the University of Texas Medical Branch at Galveston; Liamfa Shi, Weijia Nie, and Hanping Feng from Tufts University; and Bo Herman, Alfred Hausladen, and Jonathan S. Stamler from Case Western Reserve University.

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Anne Green, manager, Marketing Communications
Phone: (570) 504-9687
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