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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI073289-06
Application #
8575832
Study Section
Special Emphasis Panel (ZRG1-IDM-M (02))
Program Officer
Duncan, Rory A
Project Start
2008-06-15
Project End
2018-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$344,181
Indirect Cost
$109,181
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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