Receptor Affects Fungal Mucosal Colonization in HIV

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DESCRIPTION (provided by applicant): The oral cavity is a primary target for opportunistic infections in HIV+ patients. Histatins are a family of small molecular weight peptides secreted by human salivary glands that participate in nonimmune defense of the oral cavity. Histatin 5 (Hst-5) is the primary protective salivary component with potent antifungal properties and reduced in the saliva of AIDS patients. The receptor of Hst-5 on C. albicans cell wall was identified as heat shock protein 70. Heat shock protein 70 binds and transports the Hst-5 molecule delivering it to its cellular target. Therefore, changes in the yeast cell surface could affect the regulation of cell wall proteins and surface receptor expression. C. dubliniensis is a species that has been isolated primarily from HIV+ and AIDS patients and has the ability to rapidly develop drug resistance. In comparison to C. albicans, C. dubliniensis was shown to posses a cell wall with different morphology and composition. These properties could have aided its emergence as an opportunistic pathogen, capable of avoiding host's defense mechanisms, forming biofilms and colonizing the oral cavity. This proposal will test the hypothesis that (A) the modifications in the cell wall of C. dubliniensis consist in part of the down regulation of the receptor to Hst-5, Hsp70 which in turn reduces the susceptibility of C. dubliniensis to Hst-5 (B) oral yeast colonization by C. dubliniensis preferentially in HIV+ patients is related to decreased host salivary histatin levels and minimal fungal expression of Hsp70. Two aims are planned: 1. Determine the expression of Hsp70 in C. albicans and C. dubliniensis (a) whole cell lysates and (b) cytosolic and cell wall fractions of the yeast cell for both species and (c) Determine susceptibility to Hst-5 of C. dubliniensis and C. albicans grown at room temperature and 37 degrees C in comparison to those of C. albicans cells with extracted cell walls. 2. (a) Determine and compare the levels of salivary Hst-5 in 20 HIV+ patients with oral candidiasis (10 with C. dubliniensis and 10 with C. albicans) and in a matched healthy control group (b) Determine and compare the susceptibility to Hst-5 of the C. dubliniensis and C. albicans isolates recovered from the HIV+ individuals. Completing these aims will provide novel data extending our knowledge related to fungal infections in HIV patients. These data will help to advance our understanding of how fungal virulence factors enhance biofilm formation on oral tissues when these facors occur simultaneously with altered non specific host mucosal defenses, allowing species with proven adaptability such as C. dubliniensis to be preferentially selected.