Non-Target Site Mechanisms of Fungicide Resistance in Crop Pathogens: A Review

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.

Why do fungicide mixtures delay the evolution of resistance? An experimental evolutionary approach

“…Genetic analysis ( e.g . of the promoter of the mfs1 gene, variants of which are associated with MDR in field isolates of Z. tritici; [34]) could be performed to determine the resistance structure of evolved populations, although non-target-site resistance could also be acquired by epigenetic mechanisms [35].…”

Molecular Mechanisms Underlying Fungicide Resistance in Citrus Postharvest Green Mold

“…Two major groups of drug transporters have been characterized in fungi, including ABC (ATP-binding cassette) transporters and MFS (major facilitator superfamily) transporters. Multidrug and toxic compound extrusion (MATE), another type of transporter that has been mainly reported in bacteria [ 104 ], is related to resistance to antimicrobial agents and was recently reported to be involved in prochoraz resistance in Pd in trancriptomic analysis [ 105 ]. In this section, the general function of drug efflux transporters related to resistance to fungicides in the Pd–citrus pathosystem are reviewed ( Figure 4 ).…”

“…MBCs: methyl benzimidazole carbamates, DMIs: demethylation inhibitors; QoIs: quinone outside inhibitors; SDHIs: succinate dehydrogenase inhibitors; APs: anilinopyrimidines; PPs: phenylpyrroles. Adapted from Hu and Chen [ 105 ].…”

Evidence for the Role of CYP51A and Xenobiotic Detoxification in Differential Sensitivity to Azole Fungicides in Boxwood Blight Pathogens

“…Transcriptomics studies have reported that when exposed to antifungals, fungi with reduced azole sensitivity display increased expression of genes from the xenome, a threephase detoxification pathway found in fungi and other eukaryote lineages [19][20][21][22]. During the first phase, proteins oxidize harmful substances entering the cell [20].…”

“…In this context, cytochrome P450 monooxygenase enzymes aid metabolism of xenobiotics, such as antifungal drugs and plant secondary metabolites [20,21]. Although specific enzymes in this family can contribute to routine cellular activities/functions, such as lipid processing and synthesis of secondary metabolites, their role to aiding xenobiotic detoxification can be vital to non-target site mechanisms of tolerance to antifungals [21,22].…”