Evidence that members of the secretory aspartyl proteinase gene family, inparticular SAP2, are virulence factors for Candida vaginitis

Virulence of Candida albicans strains with targeted disruption of secretory aspartyl proteinase genes (SAP1 to SAP6) was assessed in an estrogen-depen dent rat vaginitis model. Null sap1 to sap3 but not sap4 to sap6 mutants lo st most of the virulence of their parental strain SC5314, In particular, th e sap2 mutant was almost avirulent in this model. Reinsertion of the SAP2 g ene into this latter mutant led to the to recovery of the vaginopathic pote ntial. The vaginal fluids of the animals infected by the wild type strain o r by the sap1 or sap3 mutants expressed a pepstatin-sensitive proteinase ac tivity in vitro. No traces of this activity were found in the vaginal fluid of rats challenged by the sap2 mutant. All strains were capable of develop ing true hyphae during infection. Thus, members of SAP family, in particula r SAP2, play a clear pathogenic role in vaginitis and may constitute a nove l target for chemoimmunotherapy of this infection.