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Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens

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Abstract

Azoles have been applied widely to combat pathogenic fungi in medicine and agriculture and, consequently, loss of efficacy has occurred in populations of some species. Often, but not always, resistance was found to result from amino acid substitutions in the molecular target of azoles, 14α-sterol demethylase (CYP51 syn. ERG11). This review summarizes CYP51 function, evolution, and structure. Furthermore, we compare the occurrence and contribution of CYP51 substitutions to azole resistance in clinical and field isolates of important fungal pathogens. Although no crystal structure is available yet for any fungal CYP51, homology modeling using structures from other origins as template allowed deducing models for fungal orthologs. These models served to map amino acid changes known from clinical and field isolates. We conclude with describing the potential consequences of these changes on the topology of the protein to explain CYP51-based azole resistance. Knowledge gained from molecular modeling and resistance research will help to develop novel azole structures.

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Acknowledgments

Our work received financial support from the Deutsche Forschungsgemeinschaft (DFG), the Interdisziplinäres Zentrum für Nutzpflanzenforschung, Martin-Luther-Universität Halle-Wittenberg (IZN), and BAYER CropScience GmbH. We gratefully acknowledge H. B. Deising, Director of the IZN, for his support and advice. In addition, we thank unknown reviewers for helpful comments on the manuscript.

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  1. Institut für Agrar- und Ernährungswissenschaften, Naturwissenschaftliche Fakultät III, Martin-Luther-Universität Halle-Wittenberg, Betty-Heimann-Str. 3, 06120, Halle (Saale), Germany

    Rayko Becher & Stefan G. R. Wirsel

  2. Interdisziplinäres Zentrum für Nutzpflanzenforschung, Martin-Luther-Universität Halle-Wittenberg, Betty-Heimann-Str. 3, 06120, Halle (Saale), Germany

    Stefan G. R. Wirsel

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  1. Rayko Becher
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Becher, R., Wirsel, S.G.R. Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens. Appl Microbiol Biotechnol 95, 825–840 (2012). https://doi.org/10.1007/s00253-012-4195-9

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  • DOI: https://doi.org/10.1007/s00253-012-4195-9

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