Mechanisms of Action of Ketoconazole and Voriconazole on Trichophyton rubrum: Effects on Growth, Cell Division, and Cell Membrane Morphology

Mechanisms of Action of Ketoconazole and Voriconazole on Trichophyton rubrum: Effects on Growth, Cell Division, and Cell Membrane Morphology

Onychomycosis, the infection of nails by fungal dermatophytes, affects from 3 up to 10% of the world’s population. Therefore, it is important to design an effective drug treatment for this condition. Since most onychomycosis infections are caused by theTrichophyton spp., the aim of this experiment is to study two anti-fungal drugs’, Voriconazole and Ketoconazole, minimum inhibitory concentrations (MICs) onTrichophyton rubrum (T. rubrum) . More specifically, the MICs of reference to be studied are 4, 2, 1, 0.5, 0.25, and 0.125μg.mL-1. Additionally, comparing the MIC’s of Voriconazole and Ketoconazole will improve our understanding of the separate mechanisms of action of these two azoles. After finding the most effective MICs for both drugs and comparing their effects on T. rubrum’s growth, cell division, and cell membrane morphology, a more effective drug treatment could then be proposed. This proposed drug treatment could change the morphology of microconidia, inhibit the production of ergosterol, a lipid which contributes to the fluidity of fungal cellular membranes, and consequently alter T. rubrum’s endomembrane system and rate of growth. In addition, this proposed treatment could involve a combined dosage of Voriconazole and Ketonocazole. Ultimately, this project will attempt to design a more effective treatment of onychomycosis by comparing the MIC’s of both Voriconazole and Ketoconazole on T. rubrum’s cellular growth, cell division, and cellular membrane morphology.