Tackling drug resistance with efflux pump inhibitors: from bacteria to cancerous cells

Abstract

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.

Keywords:

• ABC transporter
• prokaryotes
• eukaryotes
• evolution
• drug resistance

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors thank EMR funding (EMR/2016/001168 dated 10 March 2017) provided by Science and Engineering Research Board, Department of Science and Technology, Government of India to SN and the Infrastructure established through Department of Science and Technology, Government of India, (DST)-FIST funding (Ref No: SR/FST/ETI-331(C) provided to SASTRA Deemed to be University.