Drug:H+ antiporters in chemical stress response in yeast.
The emergence of widespread multidrug resistance (MDR) is a serious challenge for therapeutics, food-preservation and crop protection. Frequently, MDR is a result of the action of drug-efflux pumps, which are able to catalyze the extrusion of unrelated chemical compounds. This review summarizes the current knowledge on the Saccharomyces cerevisiae drug:H+ antiporters of the major facilitator superfamily (MFS), a group of MDR transporters that is still characterized poorly in eukaryotes. Particular focus is given here to the physiological role and expression regulation of these transporters, while we provide a unified view of new data emerging from functional genomics approaches. Although traditionally described as drug pumps, evidence reviewed here corroborates the hypothesis that several MFS-MDR transporters might have a natural substrate and that drug transport might occur only fortuitously or opportunistically. Their role in MDR might even result from the transport of endogenous metabolites that affect the partition of cytotoxic compounds indirectly. Finally, the extrapolation of the gathered knowledge on the MDR phenomenon in yeast to pathogenic fungi and higher eukaryotes is discussed.
Sá-Correia
Isabel
I
Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal. isacorreia@ist.utl.pt
dos Santos
Sandra C
SC
Teixeira
Miguel C
MC
Cabrito
Tânia R
TR
Mira
Nuno P
NP
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology; D017920:Antiporters / Q000378:metabolism*; D026141:Drug Resistance, Multiple, Fungal; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027361:Organic Anion Transporters; D018892:Proton-Motive Force; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D017920:Antiporters; C118429:FLR1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D029701:Saccharomyces cerevisiae Proteins