Plasticity of the MFS1 Promoter Leads to Multidrug Resistance in the Wheat Pathogen Zymoseptoria tritici

Abstract

Disease control through fungicides remains an important means to protect crops from fungal diseases and to secure the harvest. Plant-pathogenic fungi, especially Zymoseptoria tritici, have developed resistance against most currently used active ingredients, reducing or abolishing their efficacy. While target site modification is the most common resistance mechanism against single modes of action, active efflux of multiple drugs is an emerging phenomenon in fungal populations reducing additionally fungicides’ efficacy in multidrug-resistant strains. We have investigated the mutations responsible for increased drug efflux in Z. tritici field strains. Our study reveals that three different insertions of repeated elements in the same promoter lead to multidrug resistance in Z. tritici. The target gene encodes the membrane transporter MFS1 responsible for drug efflux, with the promoter inserts inducing its overexpression. These results underline the plasticity of repeated elements leading to fungicide resistance in Z. tritici.

Antifungal activity of metyltetraprole against the existing QoI‐resistant isolates of various plant pathogenic fungi

“…For the isolates of Z. tritici collected in 2015, we identified the isolates showing an MDR phenotype based on their sensitivity to tolnaftate. 14,15 As a result, 15 among 377 isolates showed reduced sensitivity to tolnaftate (EC 50 > 1.0 mg L −1 , which is 4-fold greater than the median EC 50 values of other isolates) and were considered to exhibit the MDR phenotype. Figure 4 shows the box-whisker plot for non-MDR and MDR isolates.…”

“…Furthermore, in recent years, a fungicide resistance mechanism different from the target‐site mutations has been reported in some species, including Z. tritici . It is a multi‐drug resistance (MDR) phenotype resulting from the overexpression of a multidrug transporter, such as the major facilitator superfamily (MFS) transporter in the plasma membrane . In the case of Z. tritici , the overexpression of MgMFS1 associated with the insertions to the genomic sequence upstream of its open reading frame (ORF) was detected in field isolates that showed an MDR phenotype .…”

“…In the case of Z. tritici , the overexpression of MgMFS1 associated with the insertions to the genomic sequence upstream of its open reading frame (ORF) was detected in field isolates that showed an MDR phenotype . Such isolates have been reported to show a decreased sensitivity to various classes of fungicides, regardless of their structures . Such a sensitivity shift due to the lower uptake of chemicals into the cells in an MDR phenotype should be checked for metyltetraprole because its target site is assumed to be located in the mitochondria inside the cell.…”

“…It is a multi-drug resistance (MDR) phenotype resulting from the overexpression of a multidrug transporter, such as the major facilitator superfamily (MFS) transporter in the plasma membrane. [14][15][16][17] In the case of Z. tritici, the overexpression of MgMFS1 associated with the insertions to the genomic sequence upstream of its open reading frame (ORF) was detected in field isolates that showed an MDR phenotype. 14 Such isolates have been reported to show a decreased sensitivity to various classes of fungicides, regardless of their structures.…”

“…14 Such isolates have been reported to show a decreased sensitivity to various classes of fungicides, regardless of their structures. [14][15][16][17] Such a sensitivity shift due to the lower uptake of chemicals into the cells in an MDR phenotype should be checked for metyltetraprole because its target site is assumed to be located in the mitochondria inside the cell.…”