2.A.39.3.13
Uracil-specific permease of 581 aas and 11 or 12 TMSs. FUR4.  Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungal agents when they are used simultaneously with 5-fluorouracil although the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. Subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Thus, intracellular fluorinated nucleotides play a role in azole resistance, either by preventing azoles from targeting the catalytic site of lanosterol 14-alpha-demethylase or by acting as a molecular switch for the triggering of efflux transport (Gabriel et al. 2014; ).