Candida albicans, is a member of the indigenous human flora, and is an important opportunistic pathogen. Superficial oral and vaginal irritations are the most common manifestation of C. albicans infection. More recently, severe candidosis has been recognized as a serious consequence of medical treatments such as immunosuppression or chemotherapy, and in addition, oro- esophageal infections are the most common fungal infection suffered by the AIDS patient. C. albicans is also dimorphic. This property has been exploited to examine molecular and biochemical problems related to morphogenesis as well as to gain insight concerning the pathogenesis of the organism. In these investigations we will expand our efforts in examining the contribution of plasma membrane/cell wall components to the dimorphic response, as well as to virulence, of the organism. Our approach to these issues will be to: i) Continue our analysis of relatively avirulent, cerulenin-resistant strains of C. albicans and ii) Exploit two inhibitors of germination, cerulenin and sodium butyrate, to further examine biochemical correlates of the yeast to hyphal transition. We will use these tools to: 1) Determine the organization of structural mannan/manoproteins in the avirulent mutant strains and in the parental strain, with the aim of identifying factors important in both the avirulent and cerulenin- resistant phenotype. Issues related to mannan synthesis will also be examined. 2) Investigate patterns of chitin distribution and synthesis as a function of germination, primarily through use of cerulenin and sodium butyrate. 3) Perform genetic and biochemical studies in order to define the basis of the cerulenin resistant/avirulent phenotype. We will also begin studies to investigate questions related to the contribution of polypeptides to mannoprotein structure.
| Cole, M F; Bowen, W H; Zhao, X J et al. (1995) Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis. FEMS Microbiol Lett 126:177-80 |
| McElhaney-Feser, G E; Cihlar, R L (1994) Purification and characterization of fatty acid synthase from Candida albicans strain 4918 and two derived spontaneous cerulenin-resistant mutants. J Med Vet Mycol 32:13-20 |
