Pleiotropic effects of the vacuolar ABC transporter MLT1 of Candida albicans on cell function and virulence

Among the several mechanisms that contribute to multidrug resistance (MDR), the overexpression of drug efflux pumps belonging to the ATP-binding cassette (ABC) superfamily is the most frequent cause of resistance to antifungals. The multidrug transporter proteins Cdr1p and Cdr2p of the ABCG subfamily are major players in the development of MDR in Candida albicans. Because several genes coding for ABC proteins exist in the genome of C. albicans but only Cdr1p and Cdr2p have established roles in MDR, it is implicit that the other members of the ABC family also have alternate physiological roles. This study focuses on an ABC transporter of C. albicans, Mlt1p, which is localized in the vacuolar membrane and specifically transports phosphotidylcholine (PC) into the vacuolar lumen. Transcriptional profiling of the mlt1∆/∆ mutant revealed a down-regulation of the genes involved in endocytosis, oxido-reductase activity, virulence and hyphal development. High-throughput mass spectrometry-based lipidome analysis revealed that the Mlt1p levels impact lipid homeostasis and thus lead to a plethora of physiological perturbations. These include a delay in endocytosis, inefficient sequestering of ROS, defects in hyphal development and attenuated virulence. This study is an emerging example where new and unconventional roles of an ABC transporter are being identified.