a Department of Molecular Biology and Biotechnology, University of Sheffield , Sheffield , UK.
b Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed to be University , Thanjavur , India.
Crit Rev Microbiol. 2019 May;45(3):334-353. doi: 10.1080/1040841X.2019.1607248. Epub 2019 Jun 28.
Drug resistance is a serious concern in a clinical setting jeopardizing treatment for both infectious agents and cancers alike. The wide-spread emergence of multi-drug resistant (MDR) phenotypes from bacteria to cancerous cells necessitates the need to target resistance mechanisms and prevent the emergence of resistant mutants. Drug efflux seems to be one of the preferred approaches embraced by both microbial and mammalian cells alike, to thwart the action of chemotherapeutic agents thereby leading to a drug resistant phenotype. Relative to microbes, which predominantly employs proton motive force (PMF) powered, Major Facilitator Superfamily (MFS)/Resistance Nodulation and Division (RND) classes of efflux pumps to efflux drugs, cancerous cells preferentially use ATP fuelled ATP binding cassette (ABC) transporters to extrude chemotherapeutic agents. The prevalence, evolutionary characteristics and overlapping functions of ABC transporters have been highlighted in this review. Additionally, we outline the role of ABC pumps in conferring MDR phenotype to both bacteria and cancerous cells and underscore the importance of efflux pump inhibitors (EPI) to mitigate drug resistance. Based on the literature reports and analysis, we reason out feasibility of employing bacteria as a tool to screen for EPI's targeting ABC pumps of cancerous cells.
耐药性是临床环境中一个严重的问题，会危及传染病和癌症的治疗。从细菌到癌细胞，广泛出现的多药耐药（MDR）表型，使得靶向耐药机制和防止耐药突变体的出现成为必要。药物外排似乎是微生物和哺乳动物细胞都采用的一种首选方法，以阻止化疗药物的作用，从而导致耐药表型。与主要利用质子动力势（PMF）驱动的 Major Facilitator Superfamily（MFS）/Resistance Nodulation and Division（RND）类外排泵将药物外排的微生物相比，癌细胞更倾向于利用 ATP 驱动的 ATP 结合盒（ABC）转运体来排出化疗药物。本综述强调了 ABC 转运体的普遍性、进化特征和重叠功能。此外，我们还概述了 ABC 泵在赋予细菌和癌细胞多药耐药表型中的作用，并强调了外排泵抑制剂（EPI）减轻耐药性的重要性。基于文献报道和分析，我们推断出利用细菌作为工具筛选针对癌细胞 ABC 泵的 EPI 的可行性。
