Propose is to examine global patterns of gene expression in candida albicans and neighboring host cells during commensal and opportunistic colonization of the oral mucosa. Gene expression during opportunistic infection will be examined as a function of the discrete clinical disease caused. This line of investigation represents an extension of our current efforts to characterize how different physical and chemical environmental conditions, including some of which (oxidative stress and iron deprivation) are of direct import to AIDS, that influence C. albicans mRNA profiles in vitro. In the types of analyses being used, levels of thousands of individual mRNAs are simultaneously determined by hybridization against microscopic arrays of C. albicans and, separately, human gene sequences. The results are deciphered using computer programs that cluster the information in such a way that metabolic trends are easier to identify. In cases where candida gene expression is studied in lesions (using laser capture micro dissection), adjacent tissues will also be examined for gene expression of host cells. The information gathered from this work will be complemented by concurrent efforts (in collaboration with M. Roeder's group) to define mucosal and systemic host immune responses to the specific populations of organisms studied. The goal of the proposed study is to determine whether the organism behaves differently when growing in various clinically defined settings (carrier, pseudomembranous, and erythematous), and, if so, how this difference relates to host mucosal reactions. Successful establishment of the work should result in a much more comprehensive picture of how the host and fungus interact than currently available, and may identify leads about how the organism transitions from a fungus interact than currently available, and may identify leads about how the organism transitions from a commensal to opportunistic pathogen. This line of investigation should significantly add to the knowledge base about the virulence factors of the organism,, some of which may lend themselves to the development of therapeutic measures.
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