2. Fungicide resistance

Drug resistance is known as a serious problem for the medical treatment of infections by bacteria, parasites, viruses. In agriculture, a similar situation is emerging, because rising frequencies of fungicide resistance increasingly threaten the control of major fungal diseases. Botrytis cinerea is known as a high risk organism that can rapidly develop fungicide resistance in the field. While the major fungicide resistance mechanism in fungi is target site alteration, efflux-based, so-called multidrug resistance (MDR), conferring low to intermediate resistance levels against different fungicides, can also be an important mechanism of Botrytis under field conditions (Hahn and Leroch, 2015). Two major types of MDR, involving overexpression of different drug efflux transporters, have been discovered and elucidated on the molecular level (Kretschmer et al., 2009; Hahn and Leroch, 2015). MDR1 is widely distributed in wine and strawberry fields in Europe and the Southeastern USA and of practical relevance, because it is the only resistance mechanism observed in the field against the fungicide fludioxonil. MDR1 is caused by gain-of-function mutations in a gene encoding the transcription factor Mrr1, which leads to permanent activation of its target genes and overexpression of the ABC transporter encoding gene atrB (Kretschmer et al., 2009; Fig. 1). A stronger variant of MDR1, called MDR1h, resulting in increased levels of partial resistance to fludioxonil and cyprodil, was found to be correlated with the ∆L497 mutation in mrr1 (Leroch et al., 2013).

The second MDR type, called MDR2, has been detected so far only in French and German vineyards. MDR2-related mutations, leading to overexpression of the MFS-type efflux transporter MfsM2 and partial resistance to fenhexamid and cyprodinil, have probably originated in French vineyards and then spread towards Germany (Kretschmer et al., 2009; Mernke et al., 2011). In recent years, B. cinerea populations from strawberry fields showed dramatically increased fungicide resistance frequencies and high proportions of multiresistant strains that are resistant against several or even all of the currently registered fungicides (Leroch et al., 2013; Hahn et al., 2014; Fig. 2).

Analysis of B. cinerea strawberry populations revealed the existence of different genetic groups that are distinct from the previously known B. cinerea genotypes. One of these groups, called B. cinerea S, was dominating in strawberry fields and showed a higher accumulation of fungicide resistance mutations than the common B. cinerea genotype N. In contrast, B. pse In addition, only B. cinerea S strains showed a stronger MDR1 variant called MDR1h, which confers higher levels of partial fludioxonil and cyprodinil resistance (Leroch et al., 2013; Fig. 3).


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