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Clostridium difficile is an opportunistic pathogen that typically infects patients that have been treated with broad-spectrum antibiotics. These therapies deplete the resident gut flora and allow naturally resistant C. difficile to thrive. Once established within the colon, C. difficile secretes gut-damaging toxins that can cause diarrhea and in some cases, life-threatening pseudomembranous colitis. Paradoxically, antibiotics are still used as the front-line treatment strategy for C. difficile infection (CDI). Given the obvious drawbacks of using antibiotics to treat CDI, combined with the fact that toxins are the primary determinants of virulence, there is a growing recognition that agents that inhibit toxin action (i.e., antivirulence agents) are urgently needed to effectively treat CDI. In his lecture, Dr. Melnyk will discuss his findings in this field. Using high-throughput chemical screening approaches, his group has discovered a number of toxin- and host-targeted small molecules that are capable of neutralizing the toxins of C. difficile, and in one case, prevented disease pathogenesis in infected mice. Characterization of these inhibitors has led to unexpected insights into disease pathogenesis and the interaction between host factors and virulence factors in the gut. These findings provide the foundation for new and practical pharmacological approaches to treat CDI.
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Presenter: Dr. Roman A. Melnyk
After obtaining his PhD from the Department of Biochemistry at the University of Toronto, Dr. Melnyk completed a postdoctoral fellowship at Harvard Medical School where he worked on Anthrax pathogenesis. Following this, he worked at the pharmaceutical company Merck, where he was a senior scientist within the infectious disease franchise. In 2011, Dr. Melnyk was recruited back to SickKids and the University of Toronto, where he is currently a scientist and assistant professor of Biochemsitry. Dr. Melnyk's research group is focused on understanding Clostridium difficile disease pathogenesis and in developing toxin-neutralizing therapeutics as a novel approach to treat C. difficile infection.
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