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Worldwide emergence of resistance to antifungal drugs challenges human health and food security

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Science  18 May 2018:
Vol. 360, Issue 6390, pp. 739-742
DOI: 10.1126/science.aap7999
  • Fig. 1 Current classes of drugs used against plant and animal fungal infections and known mechanisms of resistance to them.

    The six main classes of fungicides are the morpholines, which inhibit two target sites within the ergosterol biosynthetic pathway, Δ14-reductase and Δ8-Δ7-isomerase (this reduces the risk of target-site resistance, but their intrinsic antifungal activity spectrum is narrower than those of other antifungals); the azoles (used also in animal infections), which target the ergosterol biosynthetic pathway; the benzimidazoles (MBCs), which interfere with the cytoskeleton by binding to β-tubulin, thus preventing the assembly of microtubules; the strobilurins (QoIs) and succinate dehydrogenase inhibitors (SDHIs), which both inhibit the electron transfer chain of mitochondrial respiration, with the SDHIs inhibiting complex II (succinate dehydrogenase) and the QoIs inhibiting complex III (the quinone outside binding pocket of cytochrome b); and the anilinopyrimidines, which may target mitochondrial signaling pathways. Three other antifungal classes are used for animal fungal infections: the echinocandins, which inhibit cell wall biosynthesis; the pyrimidine analogs, which interfere with nucleic acid biosynthesis; and the polyenes, which bind ergosterol.

    ILLUSTRATION: CHARLOTTE GURR, ADAPTED BY K. KHOLOSKI
  • Fig. 2 Fungal species with reported antifungal resistance, by country.

    Increasing color intensity reflects a growing number of reports. The plant maps depict spatiotemporal records of resistance of crop pathogens to azoles (blue scale). The human maps depict spatiotemporal records of resistance of the pathogens A. fumigatus, C. albicans, C. auris, C. glabrata, Cryptococcus gattii, and Cryptococcus neoformans to azoles (red scale). The data are derived from peer-reviewed publications as of March 2018, reporting the occurrence of cases of resistance up to 2017 (the list of publications is available in table S1).

    ILLUSTRATION: CHARLOTTE GURR, ADAPTED BY K. KHOLOSKI
  • Fig. 3 Evolutionary drivers of antifungal resistance: heritable variation, high reproductive output, and differential survival.ILLUSTRATION: CHARLOTTE GURR, ADAPTED BY K. KHOLOSKI

Supplementary Materials

  • Worldwide emergence of resistance to antifungal drugs challenges human health and food security

    Matthew C. Fisher, Nichola J. Hawkins, Dominique Sanglard, Sarah J. Gurr

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Table S1
    • References 

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