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Newly discovered cell mechanism uses amplified nitric oxide to fight C. diff
Date:8/21/2011

CLEVELAND Aug. 21, 2011 Groundbreaking research encompassing Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, has uncovered a natural defense mechanism that is capable of inactivating the toxin that spreads Clostridium difficile, or C. diff, an increasingly common bacterial infection in hospitals and long-term care settings. The research has immediate implications for developing a new form of treatment for antibiotic-resistant bacteria.

The newly discovered mechanism involves a nitric oxide (NO)-based molecule, S-nitrosoglutathione (GSNO), which binds to the toxins secreted by C. diff bacteria to deactivate them and prevent them from penetrating and damaging cells. The mechanism encompasses S-nitrosylation (SNO), a protein modification that attaches NO to cysteine residues in enzymes and other proteins.

"We've discovered a natural defense against C. diff that is based on nitric oxide, a ubiquitous molecule that is often produced by immune cells to kill pathogens," says Jonathan Stamler, MD, director of the Institute for Transformative Molecular Medicine and the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation at the Case Western Reserve University Cardiovascular Center and University Hospitals Harrington-McLaughlin Heart & Vascular Institute. "Understanding how this mechanism deactivates toxins provides a basis for developing new therapies that can target toxins directly and thereby keep bacterial infections, like C. diff, from spreading," he says.

Dr. Stamler discovered the molecule GSNO, as well as the nitrosylation mechanism for control of protein function, in his previous research. He is one of the senior investigators studying how the protein modification inhibits the virulence of C. diff toxins. The resulting research findings appear in the Aug. 21 online issue of Nature Medicine.'/>"/>

Contact: Kevin Mayhood
kevin.mayhood@case.edu
216-368-4442
Case Western Reserve University
Source:Eurekalert

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