The virulence of strains deficient in fatty acid synthase activity by virtue of disruption/deletion of the gene was examined in a rat model of oropharyngeal candidiasis. The alleles of CA14 (Δ) were sequentially disrupted with a cassette that included a portion of from which a 984 bp fragment containing the FAS condensing reaction domain was deleted and replaced with sequences. Verification of fatty acid synthase inactivation was obtained from assays of enzyme activity. Strains in which a single allele was disrupted (CFD1 and CFD3) exhibited an approximately 20% reduction in activity, when compared to wild-type. In addition, fatty acid synthase activity was abolished in a null mutant strain (CFD2), and growth of CFD2 occurred only when the growth medium was supplemented with Tween 40 and certain fatty acids. Strain CFD2 was avirulent in the rat model, indicating that fatty acid synthase activity is required for oropharyngeal infection. Strains with a single allele disruption colonized the oral cavity, but the number of cells recovered from infected animals was approximately fivefold less than for the parental strain. The results suggest that FAS may be exploited as a possible target for the development of new antifungal agents.


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