Outwitting multidrug resistance to antifungals.
The economic cost of fungal infection and its mortality associated with multidrug resistance remain unacceptably high. Recent understanding of the transcriptional regulation of plasma membrane efflux pumps of modest specificity provides new avenues for the development of broad-spectrum fungicides. Together with improved diagnosis and indirect intervention via inhibition of the energy supply for drug efflux, we envisage multifunctional azole analogs that inhibit not only ergosterol biosynthesis and drug efflux-pump activity but also activation of the transcriptional machinery that induces drug efflux-pump expression.
Monk
Brian C
BC
Department of Oral Sciences, Faculty of Dentistry, University of Otago, Post Office Box 647, Dunedin, New Zealand.
Goffeau
Andre
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics; D005658:Fungi / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009181:Mycoses / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D026901:Membrane Transport Proteins; D014157:Transcription Factors