cDNA microarray analysis of the expression profiles of Trichophyton rubrum in response to novel synthetic fatty acid synthase inhibitor PHS11A.

Trichophyton rubrum (T. rubrum) is a major pathogen responsible for dermatophytosis. Because of potential relapse of disease with current antifungal therapy protocols, there is a need for additional and/or alternative antifungal agents for the treatment of disease caused by T. rubrum. We synthesized a potent fungal fatty acid synthase inhibitor, PHS11A, based on the structure of fungal fatty acid synthase. The antifungal activities of PHS11A were tested against 38 clinical isolates of T. rubrum and compared with those of ketoconazole and terbinafine, the MIC(50) and MIC(90) of PHS11A on the isolates were 2 and 4 microg/ml, respectively. We evaluated the transcriptional response of T. rubrum hyphae exposed to PHS11A using 11,232-spot cDNA microarrays. PHS11A exposure increased transcription of fatty acid synthases (FASs) genes FAS1 and FAS2. PHS11A also affected transcription of some genes involved in lipid metabolism, cAMP and MAPK pathways, and multidrug resistance. Quantitative real-time PCR was performed for selected genes to verify the microarray results.