Abstract
It is now well-known that the enhanced expression of ATP binding cassette (ABC) and major facilitator superfamily (MFS) proteins contribute to the development of tolerance to antifungals in yeasts. For example, the azole resistant clinical isolates of the opportunistic human fungal pathogen Candida albicans show an overexpression of Cdr1p and/or CaMdr1p belonging to ABC and MFS superfamilies, respectively. Hence, azole resistant isolates display reduced accumulation of therapeutic drug due to its rapid extrusion and that facilitates its survival. Considering the importance of major antifungal transporters, the focus of recent research has been to understand the structure and function of these proteins to design inhibitors/modulators to block the pump protein activity so that the drug already in use could again sensitize resistant yeast cells. The review focuses on the structure and function of ABC and MFS transporters of Candida to highlight the recent advancement in the field.
Highlights
The occurrence of fungal infections has risen dramatically over the past few decades because of the increase in number of immunocompromised patients undergoing, transplantation surgery, cancer chemotherapy and having an HIV infection etc. (Richardson, 2005)
Superficial infections caused by C. albicans are commonly treated with azole drugs while life-threatening systemic infections are treated with triazole drugs, or the more recent and expensive echinocandins (Perlin, 2011)
While superfamily of ATP-binding cassette (ABC) proteins are primary active transporters that employ energy from the hydrolysis of ATP to drive the efflux of drugs, those belonging to major facilitator superfamily (MFS) are secondary active transporters that utilize the electrochemical gradient of protons across the plasma membrane to efflux substrates (Cannon et al, 2009)
Summary
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. Reviewed by: Silvia Gazzin, Italian Liver Foundation (Fondazione Italiana Fegato), Italy Richard Cannon, University of Otago, New Zealand. It is well-known that the enhanced expression of ATP binding cassette (ABC) and major facilitator superfamily (MFS) proteins contribute to the development of tolerance to antifungals in yeasts. Considering the importance of major antifungal transporters, the focus of recent research has been to understand the structure and function of these proteins to design inhibitors/modulators to block the pump protein activity so that the drug already in use could again sensitize resistant yeast cells. The review focuses on the structure and function of ABC and MFS transporters of Candida to highlight the recent advancement in the field
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