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Efflux Pump Inhibitors and Their Role in the Reversal of Drug Resistance

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Antibacterial Drug Discovery to Combat MDR

Abstract

The worldwide emergence of resistant bacteria to multiple antimicrobial drugs is one of the greatest hurdles to chemotherapy. Multidrug resistance (MDR) is the capability of pathogenic bacteria to survive lethal doses of antimicrobial drugs. One of the underlying mechanisms of survival under stressful conditions is the extrusion of drugs through membrane-embedded efflux proteins. These ubiquitous resistance elements, which confer resistance or cross resistance to multiple drugs, are considered MDR efflux transporters. Consequently, efflux pump inhibitors (EPIs) from various natural and synthetic sources have been developed to increase the therapeutic armamentarium for combating bacterial resistance and restoring the antibiotic activity. Owing to less toxicity issues than chemical-based EPIs, plant-based EPIs are gaining much importance, but none are yet undergoing clinical trials. In this review, we will introduce the concept of efflux pumps and their diversity and then provide a comprehensive understanding of efflux pump inhibitors from both plant and chemical sources, their mode of action and the recent advances in their development.

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Acknowledgement

Samreen is thankful to UGC, New Delhi, for providing Non-Net Fellowship.

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Authors and Affiliations

  1. Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, India

    Samreen, Iqbal Ahmad, Faizan Abul Qais & Meenu Maheshwari

  2. School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Kendra P. Rumbaugh

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  1. Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Iqbal Ahmad

  2. Institute of Ophthalmology, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Shamim Ahmad

  3. School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Kendra P. Rumbaugh

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Samreen, Ahmad, I., Qais, F.A., Maheshwari, M., Rumbaugh, K.P. (2019). Efflux Pump Inhibitors and Their Role in the Reversal of Drug Resistance. In: Ahmad, I., Ahmad, S., Rumbaugh, K. (eds) Antibacterial Drug Discovery to Combat MDR. Springer, Singapore. https://doi.org/10.1007/978-981-13-9871-1_12

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