High aspartyl proteinase production and vaginitis in human immunodeficiency virus-infected women

Abstract

Vaginal isolates of Candida albicans from human immunodeficiency virus-positive (HIV+) and HIV- women with or without candidal vaginitis were examined for secretory aspartyl proteinase (Sap) production in vitro and in vivo and for the possible correlation of Sap production with pathology and antimycotic susceptibility in vitro. HIV+ women with candidal vaginitis were infected by strains of C. albicans showing significantly higher levels of Sap, a virulence enzyme, than strains isolated from HIV+, C. albicans carrier subjects and HIV- subjects with vaginitis. The greater production of Sap in vitro was paralleled by greater amounts of Sap in the vaginal fluids of infected subjects. In an estrogen-dependent, rat vaginitis model, a strain of C. albicans producing a high level of Sap that was isolated from an HIV+ woman with vaginitis was more pathogenic than a strain of C. albicans that was isolated primarily from an HIV-, Candida carrier. In the same model, pepstatin A, a strong Sap inhibitor, exerted a strong curative effect on experimental vaginitis. No correlation was found between Sap production and antimycotic susceptibility, as most of the isolates were fully susceptible to fluconazole, itraconazole, and other antimycotics, regardless of their source (subjects infected with strains producing high or low levels of Sap, subjects with vaginitis or carrier subjects, or subjects with or without HIV). Thus, high Sap production is associated with virulence of C. albicans but not with fungal resistance to fluconazole in HIV-infected subjects, and Sap is a potentially new therapeutic target in candidal vaginitis.

FIG. 1

Rat vaginal infection by a high-level-Sap strain (CO11; ○) isolated from the vagina of an HIV⁺ subject with vaginitis compared to the experimental infection caused by a low-level-Sap strain (SA-40) from a stock culture collection, initially isolated from the vagina of an HIV⁻ subject (□). The ● symbols indicate results with the rats challenged with the CO11 strain and cured with pepstatin A, a Sap inhibitor. Each curve represents the means (± SE) of the Candida CFU of five rats per group. All rats were still infected on day 15, when the experiment was stopped. Usually, the rats clear the infection completely in 1 month (see references and 21). Starting from day 3, there was a statistically significant difference in CFU counts between rats challenged with CO11 and the other two groups of animals. From day 6, the CFU difference between rats infected with CO11 and those infected with SA-40 strains was also significant.