Candida albicans is commonly found as a commensal organism in the oral cavity of healthy individuals and generally causes no signs of symptoms of disease. However, for patients with AIDS, the frequency of candidal disease (candidiasis) has been shown to be as high as 96%. it is known that these patients are immunodeficient and are frequently treated prophylactically with antifungal drugs. These two factors, either individually or in combination, may contribute significantly to the high percentage of candidal infections by providing an environment with selective pressures for the evolution of more virulent and possibly more life-threatening strains of Candida. Available information suggests that strain replacement may indeed be occurring in these patients, but as yet, no studies have been conducted that adequately confirm this. Using a newly developed automatic DNA fingerprinting system for assessing strain relatedness at the genetic level and several assays for assessment of virulence characteristics, the fundamental question addressed in this proposal, """"""""do commensals strains of Candida become pathogens in the transition from the asymptomatic HIV- positive state to AIDS"""""""" will be answered. If oral commensals are the source of the infecting strains in oral candidiasis, we will determine whether there is a phenotypic switch accompanying the transition. If oral commensals are replaced by pathogenic strains, we will compare the original commensal strains and the pathogenic, replacement strains for phenotypic and genotypic differences. The following Specific Aims are proposed: 1. To determine whether commensal strains subsequently become pathogenic by examining the specific genotypes of C. albicans found in: a. HIV-positive, asymptomatic individuals b. The same HIV-positive, individuals who subsequently develop AIDS and oral candidiasis Controls will include a set of commensal strains of C albicans from HIV-negative individuals int he same geographic locale and the same time window. 2. To assess differences in key physiological characteristics and virulence determinants of C. albicans (a) between its commensal strains and replacement strains and/or (b) between the commensal strains which convert to pathogens. These studies will provide significant information on the pathogenicity of Candida that could lead to improvements in diagnosis and treatment of oral candidiasis in all immunocompromised individuals.
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