| 1203 Ssa1 proteins are important virulence determinants in Candida albicans | ||
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N. NAYYAR1, S. FILLER2, N. SOLIS2, J.N. SUN1, and M. EDGERTON1, 1State University of New York - Buffalo, USA, 2University of California - Los Angeles, USA Ssa proteins are molecular chaperones that participate in a variety of cellular functions including protein folding and intracellular targeting. Candida albicans cell wall ssa proteins facilitate the fungicidal activity of salivary histatin 5, however, whether these cell wall localized proteins have further functions in Candida is unknown. Objective: To determine the role of Ssa proteins in virulence of C. albicans using ssa1Δ and ssa2Δ mutants. Methods: Virulence of ssa1Δ and ssa2Δ mutants was tested using in vivo murine models of oropharyngeal candidiasis (OPC) and systemic candidiasis. Direct cellular toxicity was evaluated in vitro by chromium release from endothelial cells exposed to C. albicans wild-type and mutant cells. The contribution of ssa proteins to cell wall assembly was evaluated by growth assays of ssa1Δ and ssa2Δ mutants under oxidative, cell wall stress, and nitrogen limiting conditions. Results: Systemic infection of mice with C. albicans ssa1Δ resulted in 100% survival rate, compared with 10 % survival of animals infected with ssa2Δ cells and 0% survival of animals infected with wild-type cells. Infection levels of OPC caused by ssa1Δ were reduced by half compared with ssa2Δ and wild type cells. Similarly, endothelial cell damage measured by chromium release was significantly reduced in the ssa1Δ strain (14.5%) compared with ssa2Δ (45%) and wild-type (37%) strains. Growth assays showed that the ssa1Δ strain was slightly more susceptible to oxidative stress conditions (hydrogen peroxide and menadione) but had no difference in sensitivity to cell wall stress conditions (calcofluor white, caffeine, hygromycin B) or nitrogen limitation compared to ssa2Δ and wild type cells. Conclusions: C. albicans ssa1 but not ssa2 proteins have an important role in virulence and development of OPC that is not related to defective cell wall assembly or resistance to host oxidative stress. Supported by USPH DE010641 from NIDCR. | ||
| Seq #129 - Clinical Diseases and Pathogenesis 3:30 PM-4:45 PM, Thursday, March 22, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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