? We propose to analyze patterns of genome-wide gene expression in C. albicans recovered from patient specimens (oral scrapings and saliva and vaginal scrapings and secretions) which display a high level of symptomatic colonization using Affymetrix GeneChip DNA microarray technology. Gene expression profiling of C. albicans will soon be widely used to characterize the molecular genetics of this model fungal pathogen as it grows in the laboratory and in relation to the expression of particular traits associated with virulence, such as yeast and hyphal morphogenesis, phenotypic switching, and response to pH, temperature, stress etc. What is acutely lacking is an understanding of which of these many potential virulence traits/markers are expressed in vivo in conjunction with symptomatic disease. The lack of correspondence and confirmation between in vitro and in vivo studies can potentially result in the accumulation of experimental data that may only be tangentially related to relevant mechanisms of pathogenesis expressed during asyrnptomatic carriage and symptomatic disease. Of greater concern, such a reliance on ex vivo experimentation is likely to fail in identifying important factors which regulate and influence pathogenesis in the infected host. This is particularly significant with respect to an organism like C. albicans, which has a vast and plastic repertoire of genes which it draws upon to rapidly adapt to changing physical environments, both in culture and by extrapolation during infection. Our overall aim is to understand what traits are important for the successful C. albicans' colonization and invasion of its vertebrate host and what particular and potentially unique virulence traits are expressed in disease presentations at these different mucosal sites. Our immediate objective will be to analyze in vivo gene expression profiles of C. albicans, the most common opportunistic pathogen associated with HIV infection and disease progression. ? ? ?
