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Infection and Immunity, June 2003, p. 3227-3234, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3227-3234.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an In Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium

Martin Schaller,1* Matthias Bein,1 Hans C. Korting,1 Stefan Baur,2 Gerald Hamm,3 Michel Monod,4 Sabine Beinhauer,5 and Bernhard Hube5

Department of Dermatology and Allergology,1 Department of Obstetrics,2 Department of Paradontology, University of Munich, Munich,3 Robert Koch-Institut, Berlin, Germany,5 Laboratoire de Mycologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland4

Received 12 November 2002/ Returned for modification 8 December 2002/ Accepted 10 March 2003

Secreted aspartyl proteinases (Saps) contribute to the ability of Candida albicans to cause mucosal and disseminated infections. A model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) was used to study the expression and role of these C. albicans proteinases during infection and tissue damage of vaginal epithelium. Colonization of the RHVE by C. albicans SC5314 did not cause any visible epithelial damage 6 h after inoculation, although expression of SAP2, SAP9, and SAP10 was detected by reverse transcriptase PCR. However, significant epithelial damage was observed after 12 h, concomitant with the additional expression of SAP1, SAP4, and SAP5. Additional transcripts of SAP6 and SAP7 were detected at a later stage of the artificial infection (24 h). Similar SAP expression profiles were observed in three samples isolated from human patients with vaginal candidiasis. In experimental infection, secretion of antigens Sap1 to Sap6 by C. albicans was confirmed at the ultrastructural level by using polyclonal antisera raised against Sap1 to Sap6. Addition of the aspartyl proteinase inhibitors pepstatin A and the human immunodeficiency virus proteinase inhibitors ritonavir and amprenavir strongly reduced the tissue damage of the vaginal epithelia by C. albicans cells. Furthermore, SAP null mutants lacking either SAP1 or SAP2 had a drastically reduced potential to cause tissue damage even though SAP3, SAP4, and SAP7 were up-regulated in these mutants. In contrast the vaginopathic potential of mutants lacking SAP3 or SAP4 to SAP6 was not reduced compared to wild-type cells. These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections.

* Corresponding author. Mailing address: Department of Dermatology and Allergology, University of Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. Phone: 49 98 5160 6151. Fax: 49 89 5160 6007. E-mail: Martin.Schaller{at}lrz.uni-muenchen.de.

Editor: T. R. Kozel

Infection and Immunity, June 2003, p. 3227-3234, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3227-3234.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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