Response of Candida albicans WT and tlo null mutant to fluconazole

This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in mitochondrial function in the tlo null mutant. Many additional cellular functions such as ergosterol biosynthesis, efflux pump regulation, and redox homeostasis were also dysregulated. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the regulation of mitochondrial function and ergosterol biosynthesis and are likely to play a role in the responses of C. albicans to azole antifungal agents.