Abstract
The rapid emergence of resistance in plant pathogens to the limited number of chemical classes of fungicides challenges sustainability and profitability of crop production worldwide. Understanding mechanisms underlying fungicide resistance facilitates monitoring of resistant populations at large-scale, and can guide and accelerate the development of novel fungicides. A majority of modern fungicides act to disrupt a biochemical function via binding a specific target protein in the pathway. While target-site based mechanisms such as alternation and overexpression of target genes have been commonly found to confer resistance across many fungal species, it is not uncommon to encounter resistant phenotypes without altered or overexpressed target sites. However, such non-target site mechanisms are relatively understudied, due in part to the complexity of the fungal genome network. This type of resistance can oftentimes be transient and noninheritable, further hindering research efforts. In this review, we focused on crop pathogens and summarized reported mechanisms of resistance that are otherwise related to target-sites, including increased activity of efflux pumps, metabolic circumvention, detoxification, standing genetic variations, regulation of stress response pathways, and single nucleotide polymorphisms (SNPs) or mutations. In addition, novel mechanisms of drug resistance recently characterized in human pathogens are reviewed in the context of nontarget-directed resistance.
Highlights
Fungicide use is a major component in the integrated disease management for crop production, especially in open fields
Two major groups of drug transporters have been characterized in fungi, including ATP-binding cassette (ABC) transporters and major facilitator superfamily (MFS) transporters
Some ABC transporters have been functionally characterized from plant pathogenic fungi (Table 1), yet the role of most remains unknown
Summary
Fungicide use is a major component in the integrated disease management for crop production, especially in open fields. The change either in the structure or the expression level of the enzyme can largely affect fungicide efficacy These target site-based resistance mechanisms have been found in many fungi with resistance to various fungicides belonging to different chemical classes [4]. Other terms such as innate or natural resistance and epigenetic resistance are used to describe certain fungal species that are insensitive to a given fungicide and transient resistance mediated by gene regulation, respectively [9,10] Some of these alternative mechanisms of resistance have not been well studied, field-resistant isolates that lacked mutations or had similar expression levels of target sites compared to sensitive isolates have been reported across pathosystems [9,11,12,13,14]. Alternative mechanisms involving drug efflux transporters, standing genetic variations, metabolic breakdown and circumvention, SNPs, RNAi-based epimutation, as well as mutator genotypes were discussed
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