Department of Biology, Brandon University, Brodie Science Building, 270-18th Street, Brandon, MB, Canada.
Parasitol Res. 2011 Nov;109(5):1311-22. doi: 10.1007/s00436-011-2378-4. Epub 2011 Apr 15.
ATP binding cassette (ABC) systems are a diverse group of proteins that have been identified in every organism, from bacteria to humans. Analysis of nematode genomes indicates that the number and arrangement of ABC systems are similar to other organisms, with the majority being ABC transporters. There are few functional studies of ABC transporters in parasitic nematodes; most reports have been on their identification or use as genetic markers to monitor drug resistance. In eukaryotes, some ABC transporters function in tissue defense by actively removing drugs, thus preventing their accumulation. The overexpression of ABC transporters that function as efflux pumps, such as P-glycoprotein (PGP) and the multidrug resistance associated protein (MRP) are known to confer resistance. Drug sensitivity can be restored by administration of PGP interfering or MDR reversal agents. The objective of this study was to determine if ABC systems in filarioid nematodes function similarly to those of other organisms. The relative expression of 33 ABC systems identified in Brugia malayi was quantified following exogenous exposure to the commonly used drug ivermectin (IVM). Following exposure of adults and microfilariae to IVM, there was a significant increase in the transcriptional profiles of a number of ABC systems, mostly within the PGP and MRP subgroups. Coadministration of PGP-interfering and MDR-reversal agents with IVM potentiated sensitivity to the drug in adults and microfilariae. The results suggest that B. malayi ABC transporters function similarly to those in other organisms and are a factor in determining drug sensitivity.
三磷酸腺苷结合盒（ABC）系统是一组多样化的蛋白质，已在从细菌到人类的所有生物中被发现。对线虫基因组的分析表明，ABC 系统的数量和排列与其他生物相似，大多数为 ABC 转运蛋白。寄生线虫中 ABC 转运蛋白的功能研究很少；大多数报道都是关于它们的鉴定或用作遗传标记来监测药物耐药性。在真核生物中，一些 ABC 转运蛋白通过主动去除药物来发挥组织防御作用，从而防止药物积累。已知功能为外排泵的 ABC 转运蛋白（如 P-糖蛋白（PGP）和多药耐药相关蛋白（MRP））的过度表达会导致耐药性。通过给予 PGP 干扰或 MDR 逆转剂可以恢复药物敏感性。本研究的目的是确定丝状线虫中的 ABC 系统是否与其他生物的 ABC 系统相似。在体外暴露于常用药物伊维菌素（IVM）后，定量测定了从班氏吴策线虫中鉴定出的 33 种 ABC 系统的相对表达量。在成虫和微丝蚴暴露于 IVM 后，许多 ABC 系统的转录谱显著增加，主要在 PGP 和 MRP 亚群中。与 IVM 一起给予 PGP 干扰和 MDR 逆转剂可增强成虫和微丝蚴对药物的敏感性。结果表明，班氏吴策线虫 ABC 转运蛋白的功能与其他生物中的 ABC 转运蛋白相似，是决定药物敏感性的一个因素。
