title: Host ABC transporter proteins may influence the efficacy of ivermectin and possibly have broader implications for the development of resistance in parasitic nematodes.
abstract: ABC transporter proteins function to extrude compounds from the cell. These proteins present an obstacle for treatment and for overcoming drug resistance as they are expressed by both host and parasite, and function similarly. The contribution of host ABC proteins to drug efficacy was examined using ivermectin and a Brugia malayi model system. Parallel in vitro and in vivo experiments were conducted using equal concentrations of ivermectin. The motilities and fecundity of B. malayi exposed to ivermectin in vitro were significantly lower than those treated in vivo. The higher motilities were correlated with low concentrations of ivermectin in worms extracted from treated hosts. The expression of ABC proteins was significantly higher in worms treated in vitro compared to those treated in vivo as well as in gerbils treated with ivermectin than in non-treated controls. The results suggest that host ABC transporters may influence the efficacy of ivermectin.
authors.affiliation: Department of Biology, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Dooley
authors.affiliation: Department of Biology, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9, Canada.
authors.forename: E A
authors.initials: EA
authors.lastname: Froese
authors.affiliation: Department of Biology, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9, Canada.
authors.forename: Y T
authors.initials: YT
authors.lastname: Chung
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Burkman
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Moorhead
authors.affiliation: Department of Biology, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9, Canada. Electronic address: ardellib@brandonu.ca.
authors.forename: B F
authors.initials: BF
authors.lastname: Ardelli
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects* / Q000502:physiology; D018076:DNA, Complementary / Q000737:chemistry; D004351:Drug Resistance; D005260:Female; D005298:Fertility / Q000187:drug effects; D005849:Gerbillinae; D007559:Ivermectin / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects; D018510:RNA, Helminth / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D011897:Random Allocation
chemical_list: D018528:ATP-Binding Cassette Transporters; D000969:Antinematodal Agents; D018076:DNA, Complementary; D018510:RNA, Helminth; D007559:Ivermectin
keywords: ABC transporter; Brugia malayi; Fecundity; Ivermectin; Motility