Studies on drug targeting in the pathogenic fungusCandida albicans: peptide transport mutants resistant to polyoxins, nikkomycins and bacilysin

Abstract

Different strains of Candida albicans show varied sensitivities to the peptide analogues bacilysin, polyoxins and nikkomycins. From a sensitive strain, B2630, spontaneous mutants were selected for resistance to each analogue; certain mutants showed cross-resistance to other analogues and associated defects in peptide transport. A bacilysin-resistant mutant was cross resistant to the other analogues and to m-fluorophenylalanyl-Ala (FPA) but retained sensitivity to m-fluorophenylalanyl-Ala—Ala (FPAA). It showed defective dipeptide transport but normal oligopeptide transport. A revertant, selected for its ability to utilize Ala-Ala as sole nitrogen source, regained wild-type dipeptide transport activity and analogue sensitivity. Thus, C. albicans has distinguishable mechanisms for dipeptide and oligopeptide transport which can be exploited for uptake of peptide-drug adducts.