Host ABC transporter proteins may influence the efficacy of ivermectin and possibly have broader implications for the development of resistance in parasitic nematodes

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...

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Bibliographic Details
Published in:	Experimental parasitology Vol. 157; pp. 35 - 43
Main Authors:	Dooley, L.A., Froese, E.A., Chung, Y.T., Burkman, E.J., Moorhead, A.R., Ardelli, B.F.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-10-2015
Subjects:	ABC transporter Animals Antinematodal Agents - pharmacology ATP-Binding Cassette Transporters - metabolism Brugia malayi Brugia malayi - drug effects Brugia malayi - physiology DNA, Complementary - chemistry Drug Resistance Fecundity Female Fertility - drug effects Gerbillinae Ivermectin Ivermectin - pharmacology Male Motility Movement - drug effects Random Allocation RNA, Helminth - analysis RNA, Helminth - genetics RNA, Helminth - isolation & purification Motility Brugia malayi ABC transporter Fecundity Ivermectin
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Summary:	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. [Display omitted] •ABC transporters function to extrude compounds from cells and are expressed by host and parasite.•Brugia malayi macrofilariae were not affected by ivermectin.•The absence of macrofilaricidal effects was associated with low amounts of ivermectin in worms.•The expression of ABC proteins was higher in worms treated in vitro and in treated gerbils.•The results suggest that host ABC transporters may influence the efficacy of ivermectin.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4894 1090-2449
DOI:	10.1016/j.exppara.2015.06.006