Control of Mycosphaerella graminicola on Wheat Seedlings by Medical Drugs Known To Modulate the Activity of ATP-Binding Cassette Transporters

Abstract

Medical drugs known to modulate the activity of human ATP-binding cassette (ABC) transporter proteins (modulators) were tested for the ability to potentiate the activity of the azole fungicide cyproconazole against in vitro growth of Mycosphaerella graminicola and to control disease development due to this pathogen on wheat seedlings. In vitro modulation of cyproconazole activity could be demonstrated in paper disk bioassays. Some of the active modulators (amitriptyline, flavanone, and phenothiazines) increased the accumulation of cyproconazole in M. graminicola, suggesting that they reversed cyproconazole efflux. However, synergism between cyproconazole and modulators against M. graminicola on wheat seedlings could not be shown. Despite their low in vitro toxicity to M. graminicola, some modulators (amitriptyline, loperamide, and promazine) did show significant intrinsic disease control activity in preventive and curative foliar spray tests with wheat seedlings. The results suggest that these compounds have indirect disease control activity based on modulation of fungal ABC transporters essential for virulence and constitute a new class of disease control agents.

Fungicide efflux and the MgMFS1 transporter contribute to the multidrug resistance phenotype in Zymoseptoria tritici field isolates

“…To understand whether the isolates classified as MDR display a resistance phenotype associated with an active fungicide efflux system, accumulation of radio‐labelled prochloraz was measured in the multidrug‐resistant strains MDR6 and MDR7 and the two sensitive strains IPO323 and S6 (Table and references therein), with and without the addition of modulators known to inhibit efflux pumps involved in MDR (Robert and Jarry, ). Amitriptyline, chlorpromazine and verapamil were chosen for their proven activity in Z. tritici (Roohparvar et al ., ; Leroux and Walker, ).…”

The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana

“…The broad substrate specificity of BcatrB may help the fungus to cause disease on other host plants than Arabidopsis, and extend its host range to comprise crop plants such as grapevine. It might thus be a possible target for fungicides as suggested for other transporters (Reimann and Deising, 2005; Roohparvar et al. , 2007); modulators of transporter function can be used to increase the susceptibility of plant pathogenic fungi to fungitoxic compounds (Hayashi et al.…”

Constraints on the evolution of azole resistance in plant pathogenic fungi

“…For example, genes encoding ABC or MFS transporters have been identified in plant pathogenic fungi, and their capacity to export azoles by heterologous expression and targeted knockout studies has been demonstrated (de Waard et al ., ). Genome‐wide transcriptional studies have identified ABC transporter genes responsive to azole treatment (Becher et al ., ), and the use of putative chemical efflux antagonists has shifted resistant phenotypes, as well as sensitizing wildtype isolates (Roohparvar et al ., ; Leroux & Walker, ). Yet, although MDR phenotypes of plant pathogens, including M. graminicola and Oculimacula yallundae , have been proposed to impact on fungicide performance (Table ; Leroux & Walker, ; Leroux et al ., ), to date, only in Botrytis cinerea has a genetic mechanism conferring enhanced efflux to multiple fungicides been characterized and shown to impact on the performance of fungicides in the field (Table ; Kretschmer et al ., ).…”