期刊
PARASITOLOGY INTERNATIONAL
卷 62, 期 6, 页码 639-646出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.parint.2013.02.008
关键词
ABC systems; ABC transporter; Drug resistance; Nematode; P-glycoprotein
类别
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Canada Foundation for Innovation (CFI)
- Manitoba Health Research Council (MHRC)
- Manitoba Research and Innovation Fund (MRIF)
- National Institutes of Health
- C. elegans Reverse Genetics Core Facility at the University of British Columbia
- Canadian Institutes for Health Research
- Genome Canada
- Genome BC
- Michael Smith Foundation
The completion of a number of nematode genomes has provided significant information on ABC systems in these organisms. Nematodes have more ABC systems genes and greater diversity than do mammalian species. Class 1 and class 2 ABC systems, more commonly known as ABC transporters, are present. As in other organisms, nematode ABC systems are characterized by a highly conserved ATP-binding domain (ABC_2) and a less conserved transmembrane domain (ABC_TM1/TM1F). Studies of drug resistance in nematodes have suggested that ABC transporters are part of the resistance mechanism. Evidence in support of this has been obtained from genetic studies where an association between anthelmintic selection and ABC transporters was shown by comparisons between unselected and drug selected, or resistant, populations of parasitic nematodes. In drug resistant populations, genetic polymorphism and diversity, genotype patterns, and linkage disequilibrium were disrupted. Multidrug resistance (MDR) reversing agents that inhibit ABC function improve efficacy in sensitive nematode populations and restore sensitivity in resistant populations. Similar to the situation in clinical oncology, overexpression of ABC systems occurs in drug resistant and sensitive populations following drug exposure, particularly those in the P-glycoprotein (PGP) subfamily. Deletion or disruption of ABC genes, particularly PGP and the multidrug resistance associated protein (MRP), increases sensitivity to some drugs, particularly ivermectin. These studies provide evidence that ABC transporters play a role in drug action and resistance in nematodes. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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