Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence.
Drug transporters are membrane proteins that provide protection for organisms against natural toxic products and fungicides. In plant pathogens, drug transporters function in baseline sensitivity to fungicides, multidrug resistance (MDR) and virulence on host plants. This paper describes drug transporters of the filamentous fungi Aspergillus nidulans (Eidam) Winter, Botrytis cinerea Pers and Mycosphaerella graminicola (Fückel) Schroter that function in fungicide sensitivity and resistance. The fungi possess ATP-binding cassette (ABC) drug transporters that mediate MDR to fungicides in laboratory mutants. Similar mutants are not pronounced in field resistance to most classes of fungicide but may play a role in resistance to azoles. MDR may also explain historical cases of resistance to aromatic hydrocarbon fungicides and dodine. In clinical situations, MDR development in Candida albicans (Robin) Berkhout mediated by ABC transporters in patients suffering from candidiasis is common after prolonged treatment with azoles. Factors that can explain this striking difference between agricultural and clinical situations are discussed. Attention is also paid to the risk of MDR development in plant pathogens in the future. Finally, the paper describes the impact of fungal drug transporters on drug discovery.
Laboratory of Phytopathology, Wageningen University, Binnenhaven 5, NL-6709 PD Wageningen, The Netherlands. maarten.dewaard@wur.nl
Maarten A
MA
de Waard
Alan C
AC
Andrade
Keisuke
K
Hayashi
Henk-Jan
HJ
Schoonbeek
Ioannis
I
Stergiopoulos
Lute-Harm
LH
Zwiers
D000383:Agriculture; D001203:Ascomycota / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D001233:Aspergillus nidulans / Q000187:drug effects* / Q000502:physiology; D005075:Biological Evolution; D020171:Botrytis / Q000187:drug effects* / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D026141:Drug Resistance, Multiple, Fungal / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000502:physiology*; D010935:Plant Diseases
D005656:Fungal Proteins; D005659:Fungicides, Industrial; D027425:ATP-Binding Cassette, Sub-Family C Proteins