Impact of mutations in the CYP51 gene of Mycosphaerella graminicola on azole fungicide sensitivity and intrinsic protein function

In the current absence of fully resistant wheat cultivars, control of Mycosphaerella gramini-cola relies on the programmed application of fungicides. In the past, the fungus has readily adapted to chemicals used for its control so that at present, the main group of effective site-specific fungicides on the market are the azoles (imidazoles and triazoles). However, there has been a recent decline in the efficacy of some azole fungicides against M. graminicola, to the extent that some previously efficacious fungicides are no longer recommended to control the disease. However, some azoles are less affected by this shift in sensitivity and remain products of choice, although there is concern that owing to the selection pressures imposed by increased azole use, resistance to all azoles is now a possibility. The molecular changes underlying altered azole sensitivity are best understood in resistant strains of opportunistic human pathogenic fungi, in particular Candida albicans, which can cause major clinical problems in immuno-compromised patients. In C. albicans two mechanims of resistance predominate, mutations in the target-encoding gene (CYP51), and up-regulation of efflux pumps which reduce intracellular azole concentration. These are generally found to combine, conferring a stepwise increase in resistance levels. In M. graminicola, similar mechanisms