In vivo expression and localization of Candida albicans secreted aspartyl proteinases during oral candidiasis in HIV-infected patients

Isoforms of aspartyl proteinase (Sap), which are encoded by at least nine r elated SAP genes, have been implicated to be a major virulence factor of th e opportunistic yeast Candida albicans in experimental infections. Although it is generally assumed that proteinases are important for infections, det ailed information on the pathogenetic role of Saps is still lacking. The sa me applies to the question whether the genes and corresponding isoforms of the enzyme are expressed during oral infection. For in vivo investigations, parts of the lesional oral epithelium were collected from three HIV-infect ed patients with oropharyngeal candidiasis. Immunoelectron microscopy was p erformed (pre- and post-embedding gold labeling with silver enhancement) us ing an anti-Sap murine monoclonal antibody directed against the gene produc ts Sap1-3. It was possible to demonstrate expression of Sap antigens in eac h of the three samples of human oral candidiasis. This suggests that at lea st one of the genes SAP1-3 was expressed at the time of sample collection. Furthermore, a possible role of the enzymes during the interaction of yeast cells and mucosal cells is suggested: the majority of Sap antigens is secr eted by those C. albicans cells that adhere directly to the epithelial surf ace. Sap immunoreactivity can be detected in particular at the site of clos e contact between C. albicans and epithelial cells, suggesting a pathogenet ic role of the Saps in host-fungal interaction. Thus, inhibition of the enz yme might prove to be an important alternative in the prevention and treatm ent of candidiasis.