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ABC转运蛋白在寄生线虫生存中的重要性及新型控制策略的开发前景

Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies.

作者信息

Raza Ali, Williams Andrew R, Abeer Muhammad Mustafa

机构信息

Queensland Alliance for Agriculture & Food Innovation, Centre for Animal Science, The University of Queensland, St Lucia, QLD 4067, Australia.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Frederiksberg, Denmark.

出版信息

Pathogens. 2023 May 24;12(6):755. doi: 10.3390/pathogens12060755.

Abstract

ABC transporters, a family of ATP-dependent transmembrane proteins, are responsible for the active transport of a wide range of molecules across cell membranes, including drugs, toxins, and nutrients. Nematodes possess a great diversity of ABC transporters; however, only P-glycoproteins have been well-characterized compared to other classes. The ABC transport proteins have been implicated in developing resistance to various classes of anthelmintic drugs in parasitic nematodes; their role in plant and human parasitic nematodes still needs further investigation. Therefore, ABC transport proteins offer a potential opportunity to develop nematode control strategies. Multidrug resistance inhibitors are becoming more attractive for controlling nematodes due to their potential to increase drug efficacy in two ways: (i) by limiting drug efflux from nematodes, thereby increasing the amount of drug that reaches its target site, and (ii) by reducing drug excretion by host animals, thereby enhancing drug bioavailability. This article reviews the role of ABC transporters in the survival of parasitic nematodes, including the genes involved, their regulation and physiological roles, as well as recent developments in their characterization. It also discusses the association of ABC transporters with anthelmintic resistance and the possibility of targeting them with next-generation inhibitors or nutraceuticals (e.g., polyphenols) to control parasitic infections.

摘要

ABC转运蛋白是一类依赖ATP的跨膜蛋白家族,负责多种分子跨细胞膜的主动运输,包括药物、毒素和营养物质。线虫拥有种类繁多的ABC转运蛋白;然而,与其他类别相比,只有P-糖蛋白得到了充分的表征。ABC转运蛋白与寄生线虫对各类驱虫药物产生抗性有关;它们在植物寄生线虫和人类寄生线虫中的作用仍需进一步研究。因此,ABC转运蛋白为制定线虫控制策略提供了一个潜在的机会。多药抗性抑制剂正变得越来越有吸引力用于控制线虫,因为它们有可能通过两种方式提高药物疗效:(i)限制线虫的药物外排,从而增加到达其靶位点的药物量;(ii)减少宿主动物的药物排泄,从而提高药物的生物利用度。本文综述了ABC转运蛋白在寄生线虫生存中的作用,包括相关基因、它们的调控和生理作用,以及它们表征方面的最新进展。它还讨论了ABC转运蛋白与驱虫抗性的关联,以及用下一代抑制剂或营养保健品(如多酚)靶向它们以控制寄生虫感染的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d2a/10300789/3d421d54fd7d/pathogens-12-00755-g001.jpg

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