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Emerging Antifungal Drug Resistance in Aspergillus fumigatus and Among Other Species of Aspergillus

  • Fungal Genomics and Pathogenesis (S Shoham, Section Editor)
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Abstract

Purpose of Review

The purpose of this review is to give an overview of recent findings on antifungal resistance in Aspergillus fumigatus (the major causative agent of aspergillosis) and sibling Aspergillus species, which can be hidden agents of aspergillosis.

Recent Findings

Azole resistance by Cyp51A mutation in A. fumigatus is a growing problem worldwide. The resistance can occur in patients or in the environment. The former occurs by drug selection in the host, inducing mutations in Cyp51A. The latter is characterized by a tandem repeat in the promoter region of cyp51A gene and mutation(s) in Cyp51A. Environmental resistant strains are prevailing rapidly and globally. Moreover, efflux pump and biofilm formation are closely related with antifungal resistance of A. fumigatus. Finally, sibling species of Aspergillus are described with regard to antifungal resistance.

Summary

Environmental azole-resistant strains have newly emerged and been dispersed globally, and continuous survey and countermeasures are urgently needed against these strains. Although the contributions of Cyp51A and efflux pumps to antifungal resistance are becoming clear, other resistance mechanisms remain unclear. Further investigations including genome comparisons will help to clarify the novel resistant mechanisms and to develop countermeasures or novel antifungal drugs against resistant strains of A. fumigatus and other Aspergillus species that have low susceptibility to antifungal therapeutics.

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Acknowledgments

The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by AMED under Grant Numbers JP18jm0110015, JP19fm0208024, and JP18fk0108208.

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Authors and Affiliations

  1. Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan

    Takahito Toyotome

  2. Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan

    Takahito Toyotome

  3. Medical Mycology Research Center, Chiba University, Chiba, Japan

    Takahito Toyotome, Daisuke Hagiwara, Hiroki Takahashi, Akira Watanabe & Katsuhiko Kamei

  4. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan

    Daisuke Hagiwara

  5. Molecular Chirality Research Center, Chiba University, Chiba, Japan

    Hiroki Takahashi

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  1. Takahito Toyotome
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Correspondence to Takahito Toyotome.

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Katsuhiko Kamei declares grants from Pfizer, Astellas, Dainihon-Sumitomo Pharma, MSD, and Ninon Nohyaku; and honoraria from Astellas, Pfizer, MSD, Dainihon-Sumitomo Pharma, AstraZeneca, and Janssen.

Akira Watanabe declares grants from Astellas, AstraZeneca, MSD, Dainihon-Sumitomo, Beckman Coulter, Tashio Toyama Pharma, and Maruho Co; and has served as a supervisor for Pfizer and Astellas.

Takahito Toyotome, Daisuke Hagiwara, and Hiroki Takahashi declare that they have no competing interests.

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Toyotome, T., Hagiwara, D., Takahashi, H. et al. Emerging Antifungal Drug Resistance in Aspergillus fumigatus and Among Other Species of Aspergillus. Curr Fungal Infect Rep 12, 105–111 (2018). https://doi.org/10.1007/s12281-018-0318-9

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