Molecular aspects of azole antifungal action and resistance.
During the past three decades azole compounds have been developed as medical and agricultural agents to combat fungal diseases. During the 1980s they were introduced as orally active compounds in medicine and the number of such azole drugs is likely to expand in the near future. They represent a successful strategy for antifungal development, but as the incidence of fungal infection has increased coupled to prolonged use of the drugs, the (almost) inevitable emergence of resistance has occurred. This was after resistance had already been encountered as a serious problem in the field, where a larger number of azole fungicides had been employed commercially. In this review the molecular basis of how azoles work is discussed together with how fungi overcome the inhibitory effect of these compounds: through alterations in the primary target molecule (cytochrome P45051; Erg11p; sterol 14alpha-demethylase); through drug efflux mechanisms and through a suppressor mechanism allowing growth on 14-methylated sterols. Copyright 1999 Harcourt Publishers Ltd.
Lamb
David
D
Cytochrome P450 Research Group, AberBiocentre, Edward Llwyd Building, University of Wales Aberystwyth, Aberystwyth, SY23 3DA, Wales, UK
Kelly
Diane
D
Kelly
Steven
S