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Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

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Abstract

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.

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Acknowledgments

This work was supported by a Discovery Project from the Australian Research Council (ARC, DP120102694). B. H. was supported by an Australian Postgraduate Award. Work in the A.T. lab on C. albicans is funded by the Australian National Health and Medical Research Council (NHMRC), and the Monash University Researcher Accelerator (MRA) Grant.

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Authors and Affiliations

  1. La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia

    Brigitte M. E. Hayes, Marilyn A. Anderson, Nicole L. van der Weerden & Mark R. Bleackley

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia

    Ana Traven

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  1. Brigitte M. E. Hayes
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  2. Marilyn A. Anderson
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  3. Ana Traven
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  4. Nicole L. van der Weerden
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  5. Mark R. Bleackley
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Correspondence to Nicole L. van der Weerden or Mark R. Bleackley.

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N. L. van der Weerden and M. R. Bleackley contributed equally.

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Hayes, B.M.E., Anderson, M.A., Traven, A. et al. Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins. Cell. Mol. Life Sci. 71, 2651–2666 (2014). https://doi.org/10.1007/s00018-014-1573-8

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  • DOI: https://doi.org/10.1007/s00018-014-1573-8

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