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Journal of Clinical Microbiology, May 1999, p. 1376-1380, Vol. 37, No. 5
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

High Aspartyl Proteinase Production and Vaginitis in Human Immunodeficiency Virus-Infected Women

F. de Bernardis,1 F. Mondello,1 G. Scaravelli,2 A. Pachì,2 A. Girolamo,1 L. Agatensi,3 and A. Cassone1,*

Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità,1 Clinic of Obstetrics and Gynecology of the Università La Sapienza,2 and Complesso Ospedaliero San Filippo Neri, Presidio Sant'Andrea,3 Rome, Italy

Received 9 December 1998/Returned for modification 30 January 1999/Accepted 17 February 1999

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.

* Corresponding author. Mailing address: Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Phone: 39.6.49387113. Fax: 39.6.49902934. E-mail: cassone{at}iss.it.

Journal of Clinical Microbiology, May 1999, p. 1376-1380, Vol. 37, No. 5
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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