Journal
EXPERIMENTAL PARASITOLOGY
Volume 129, Issue 2, Pages 137-144Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2011.06.018
Keywords
Brugia malayi; ABC transporter superfamily; Moxidectin; Overexpression; P-glycoprotein Multidrug resistance protein; Drug resistance
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Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Canada Foundation for Innovation
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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. (C) 2011 Elsevier Inc. All rights reserved.
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