MITOGEN-ACTIVATED PROTEIN KINASE-DEFECTIVE CANDIDA-ALBICANS IS AVIRULENT IN A NOVEL MODEL OF LOCALIZED MURINE CANDIDIASIS

Candida albicans strains with a deletion of the mitogen-activated prot ein kinase CEK1 gene are defective in the yeast to hyphal transition o n solid surfaces in vitro. The virulence of a cek1 Delta/cek1 Delta nu ll mutant strain was compared with its wild-type parent strain (WT) in a novel model of localized candidiasis. The mammary glands of lactati ng mice (at day 5 postpartum) were infected for 2, 4 and 6 days with 5 0 mu l suspension containing 1 x 10(5), 1 x 10(6) and 1 x 10(7) blasto spores before death. Infected and non-infected control glands were eva luated pathologically, All animals infected with cek1 Delta/cek1 Delta null mutant strains showed no lesions while 65% of animals infected w ith the WT strain had severe lesions characterized by widespread heter ophilic infiltration, necrosis, and abscess formation. As an additiona l control, animals infected with the disrupted strain complemented wit h the WT CEK1, on a replicating plasmid, also showed severe pathologic al changes similar to the WT strain. These results clearly demonstrate that the CEK1 gene codes for a virulence determinant of C. albicans a nd that the mouse mastitis model is well suited for the discriminative study of the pathogenicity of different C. albicans strains. (C) 1998 Federation of European Microbiological Societies. Published by Elsevi er Science B.V. All rights reserved.