title: ABC transporters influence sensitivity of Brugia malayi to moxidectin and have potential roles in drug resistance.
abstract: Some ABC transporters play a significant role in human health and illness because they confer multidrug resistance (MDR) through their overexpression. Compounds that inhibit the drug efflux mechanism can improve efficacy or reverse resistance. Of the eight described ABC transporter subfamilies, those proteins conferring MDR in humans are in subfamilies A, B, C, and G. In nematodes, transporters in subfamilies B and C are suggested to confer resistance to ivermectin. The Brugia malayi ABC transporter superfamily was examined to assess their potential to influence sensitivity to moxidectin. There was an increase in expression of ABC transporters in subfamilies A, B, C, and G following treatment. Co-administration of moxidectin with inhibitors of ABC transporter function did not enhance sensitivity to moxidectin in males; however, sensitivity was significantly enhanced in females and microfilariae. The work suggests that ABC transporters influence sensitivity to moxidectin and have a potential role in drug resistance.
authors.affiliation: Department of Biology, Brandon University, Brandon, Manitoba, Canada.
authors.forename: L E
authors.initials: LE
authors.lastname: Stitt
authors.forename: J B
authors.initials: JB
authors.lastname: Tompkins
authors.forename: L A
authors.initials: LA
authors.lastname: Dooley
authors.forename: B F
authors.initials: BF
authors.lastname: Ardelli
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000969:Antinematodal Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D018942:Macrolides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D050257:Tubulin Modulators / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D000969:Antinematodal Agents; D002121:Calcium Channel Blockers; D018942:Macrolides; D050257:Tubulin Modulators; D014747:Vinblastine; D014700:Verapamil; C027837:moxidectin; D003630:Daunorubicin