One of Candida albicans most impressive virulence attributes is the ability to propagate as a biofilm when attached to a medical device, such as a venous catheter. This critical factor alone is responsible for the majority of invasive and persistent disease. As conventional antimicrobials are ineffective for treatment of these life-threatening infections, further understanding of the biofilm lifestyle and how the cells survive drug therapy is desperately needed. The microbe-derived extracellular matrix, a distinguishing feature of biofilms, has been linked to several roles in biofilm pathogenesis. The proposed investigation capitalizes on our progress during the last funding period that identified the role o one matrix component, ?-1,3 glucan, for biofilm resistance and dispersion. Our excitement for future investigation is based upon two unexpected observations. First, we were surprised to find an abundance of two additional matrix polysaccharides, ?-1,6 glucan and ?-mannan. Second, we demonstrated an interaction among these matrix components. Our major objectives now are 1] to define the genetic pathways governing production, delivery, and maturation of the entire complement of polysaccharide matrix and 2] to discern how these matrix components function both individually and in a coordinated fashion during biofilm pathogenesis.

Public Health Relevance

Candida frequently forms biofilms on the surface of medical devices. There are no effective drug therapies for these commonly lethal fungal infections. The proposed studies will uncover mechanisms that permit Candida to proliferate on implanted devices despite extraordinarily high drug concentrations. Our goal is to discover targets for development of innovative therapeutic agents.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-M (02))
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Duncan, Rory A
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University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
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