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Finding the needle in a haystack: Mapping antifungal drug resistance in fungal pathogen by genomic approaches

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Fungi are ubiquitous on earth and are essential for the maintenance of the global ecological equilibrium. Despite providing benefits to living organisms, they can also target specific hosts and inflict… Click to show full abstract

Fungi are ubiquitous on earth and are essential for the maintenance of the global ecological equilibrium. Despite providing benefits to living organisms, they can also target specific hosts and inflict damage. These fungal pathogens are known to affect, for example, plants and mammals and thus reduce crop production necessary to sustain food supply and cause mortality in humans and animals. Designing defenses against these fungi is essential for the control of food resources and human health. As far as fungal pathogens are concerned, the principal option has been the use of antifungal agents, also called fungicides when they are used in the environment. Commercial antifungal agents and fungicides belong to several classes and affect several cellular functions (Fig 1) [1]. Fungicides outnumber medical antifungal agents by the number of chemical classes and by the number of licensed drugs [1]. Exposing plant and/or human pathogens to these agents results in a substantial fungal growth deficiency and eventually clearance of the pathogens in the infected sites or infected host. However, the same exposure imposes strong selective pressures for the development of resistance, which is ineluctably acquired over shortand long-term periods. Fungicides that are spread in the environment can also cause the selection of resistance in ubiquitous fungi that are also human pathogens. The transmission of environmentally acquired resistance to human is of concern because it reduces the limited number of possible treatments to a few alternatives. It is important to resolve resistance mechanisms because they may highlight not only novel biology but also may reveal novel strategies to counteract and combat resistance. Resistance mechanisms can be grouped in at least three general principles that include (i) decrease of effective intracellular drug concentration, (ii) alterations of the drug target, and (iii) compensatory mechanisms which decrease drug toxicity [2]. I will summarize here approaches that led to the understanding of antifungal resistance in plant and human fungal pathogens with a special focus on genome-wide studies.

Keywords: antifungal agents; finding needle; fungal pathogens; drug; resistance; needle haystack

Journal Title: PLoS Pathogens
Year Published: 2019

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