Coordinate control of lipid composition and drug transport activities is required for normal multidrug resistance in fungi.
Pathogenic fungi present a special problem in the clinic as the range of drugs that can be used to treat these types of infections is limited. This situation is further complicated by the presence of robust inducible gene networks encoding different proteins that confer tolerance to many available antifungal drugs. The transcriptional control of these multidrug resistance systems in several key fungi will be discussed. Experiments in the non-pathogenic Saccharomyces cerevisiae have provided much of our current understanding of the molecular framework on which fungal multidrug resistance is built. More recent studies on the important pathogenic Candida species, Candida albicans and Candida glabrata, have provided new insights into the organization of the multidrug resistance systems in these organisms. We will compare the circuitry of multidrug resistance networks in these three organisms and suggest that, in addition to the well-accepted drug efflux activities, the regulation of membrane composition by multidrug resistance proteins provides an important contribution to the resistant phenotypes observed.
Shahi
Puja
P
Department of Molecular Physiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Moye-Rowley
W Scott
WS
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D002176:Candida albicans / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D026141:Drug Resistance, Multiple, Fungal / Q000502:physiology*; D005800:Genes, Fungal / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D013107:Sphingolipids / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D008055:Lipids; C085480:PDR1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D014157:Transcription Factors; C481277:Yrr1 protein, S cerevisiae