Strategies to Combat Bacterial Antimicrobial Resistance: a Focus on Mechanism of the Efflux Pumps Inhibitors

Abstract

The surge in multidrug resistance (MDR) in the bacterial system has constricted the use of foregoing therapeutics for the treatment of fatal infections. The primary factor responsible for the ineffectiveness of these antibiotics is their continuous extrusion out of the bacterial cells via efflux pumps. Overexpression of efflux pumps contributes to both intrinsic and acquired resistance in bacteria. Therefore, efflux pumps can be the potential target to fight MDR. Use of efflux pump inhibitors (EPIs) alone or in combination with existing drug/antibiotics would not only help in combating the resistance but also prove to be a cost-effective approach as it makes the existing therapeutics effective. In this review, we have discussed all the possible therapeutic strategies for the development of potent EPIs. This includes plant- and microbe-derived EPIs and nanomaterial-based EPIs. The molecular targets (i.e., efflux pumps) and target organisms for these EPIs have also been discussed. Besides, this review also highlights the different methods to investigate active EPIs and their biological significance. The present study aims at exploiting the anti-efflux property of these compounds and developing potent therapeutics for the treatment of fatal bacterial infections.

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Data Availability

All the data are available in the manuscript and its supplementary data

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Acknowledgements

MT wants to thank the Central University of Rajasthan for the Ph.D. fellowship. PV wants to thank CSIR (Ref: 09/1131(0031)/2019-EMR-I) for Ph.D. fellowship.

Funding

This study is funded by Science and Engineering Research Board (SERB), India, for Core Research Grant (Ref: EMR/2017/001854/HS).

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Conceived and designed the experiments: V.T., Data collection: P.V. Analyzed the data: P.V., and V.T., Wrote the manuscript: P.V. and M.T., Proofread of the final version: P.V., M.T., and V.T.

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Correspondence to Vishvanath Tiwari.

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Verma, P., Tiwari, M. & Tiwari, V. Strategies to Combat Bacterial Antimicrobial Resistance: a Focus on Mechanism of the Efflux Pumps Inhibitors. SN Compr. Clin. Med. (2021). https://doi.org/10.1007/s42399-021-00780-z

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Keywords

  • Multidrug resistance
  • Bacterial efflux pumps
  • Plant and microbe-derived EPIs
  • Metal nanoparticles as EPIs