Candida albicans secreted aspartyl proteinases.

Abstract

Evidence suggests that infections with the opportunistic yeast Candida albicans are caused by several factors. Among these virulence attributes, secreted aspartyl proteinases (Saps) are widely believed to play a role during pathogenesis. Sap isoenzymes are encoded by at least eight closely related SAP genes. Antigen-antibody studies provided evidence that Sap isoenzymes are expressed in vivo and experimental infections with proteinase deficient mutants suggested a role for Saps in the virulence of C. albicans. However, only one gene product, Sap2, has been characterized in detail. In vitro studies with purified Sap(2) suggested several possible host targets but the role of each Sap isoenzyme remains unclear. The expression pattern of SAP genes proposed that Sap isoenzymes are secreted simultaneously with morphological changes such as the yeast to hyphal transition or during phenotypic switching. In addition, extracellular proteolytic activity may affect adhesion to host cells and thus may help the fungus to persist on host surfaces and to penetrate into deeper tissue. This review will deal with secretory proteinases from C. albicans as putative virulence factors and will focus on the more recent molecular aspects of the proteinases and their genes. Insights into the genetic organization and regulation of the secreted proteinases suggest not only that these enzymes may act as virulence factors of C. albicans, but that the pathogenesis of this fungus is indeed complex and multifactorial.