title: 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.
authors.affiliation: Laboratory of Phytopathology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Ramin
authors.initials: R
authors.lastname: Roohparvar
authors.forename: Aurelie
authors.initials: A
authors.lastname: Huser
authors.forename: Lute-Harm
authors.initials: LH
authors.lastname: Zwiers
authors.forename: Maarten A
authors.initials: MA
authors.lastname: De Waard
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000930:Antidiarrheals / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001203:Ascomycota / Q000187:drug effects* / Q000254:growth & development; D018492:Dopamine Antagonists / Q000494:pharmacology; D004357:Drug Synergism; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal; D008139:Loperamide / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010935:Plant Diseases / Q000382:microbiology; D011395:Promazine / Q000494:pharmacology; D036226:Seedlings / Q000382:microbiology*; D014230:Triazoles / Q000494:pharmacology; D014908:Triticum / Q000382:microbiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D018759:Adrenergic Uptake Inhibitors; D000930:Antidiarrheals; D000935:Antifungal Agents; D018492:Dopamine Antagonists; D005656:Fungal Proteins; D014230:Triazoles; D000639:Amitriptyline; C093628:cyproconazole; D008139:Loperamide; D011395:Promazine