The investigator proposes in this renewal application to continue the study of the role(s) of secreted aspartyl proteinases (Saps) in Candida infections of HIV infected individuals. In healthy individuals these infections are commensal but in people that are immunocompromised they are pathogenic. It is proposed that Saps are important virulence factors and that a further understanding of this family of related enzymes will suggest novel approaches for treating Candida infections. The proposed experiments fall into two categories. In the first, an analysis of the regulatory mechanisms that govern SAP gene expression will be undertaken. Experiments will focus on the promoter regions of the SAP genes and on the recently cloned KEX2 gene product, which likely plays a role in the maturation and secretion of Saps. In the second part of the application, SAP expression in AIDS patient samples will be evaluated in an attempt to define which Saps are more important in vivo. It is anticipated that these experiments will lead to the use of animal models.
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