CORRELATION BETWEEN RHODAMINE-123 ACCUMULATION AND ATOLE SENSITIVITY IN CANDIDA SPECIES - POSSIBLE ROLE FOR DRUG EFFLUX IN DRUG-RESISTANCE

A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell. We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part to active drug efflux. Rhodamine 123 (Rh123) is a fluorescent compound that is transported by a wide v ariety of MDR cell types, We have shown that certain azole-resistant s trains of Candida albicans, C. glabrata, and C. krusei accumulate less Rh123 than azole-susceptible ones, In C. albicans, Rh123 accumulation was growth phase and temperature dependent and was increased by proto n uncouplers and by reserpine, an MDR modulator, This is consistent wi th an energy-dependent efflux mechanism for Rh123, mediated by an MDR transporter, In C. glabrata, but not in C. albicans, there was competi tion between Rh123 and fluconazole for efflux. Thus, in C. glabrata, R h123 and fluconazole appear to be transported via a common MDR-like tr ansporter, whereas in C. albicans, the Rh123 transporter does not appe ar to transport azoles.