Microbial efflux systems and inhibitors: Approaches to drug discovery and the challenge of clinical implementation

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Kourtesi, Christina, Ball, Anthony R., Huang, Ying-Ying, Jachak, Sanjay M., Vera, D. Mariano A., Khondkar, Proma, Gibbons, Simon, Hamblin, Michael R. and Tegos, George P. (2013) Microbial efflux systems and inhibitors: Approaches to drug discovery and the challenge of clinical implementation. Open Microbiology Journal, 7 (Suppl. 1). pp. 34-52. ISSN 1874-2858

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Abstract

Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.

Item Type:	Article
Uncontrolled Keywords:	antimicrobial resistance,biofilms,dual action antimicrobials,multidrug efflux systems,natural efflux pump inhibitors,photo inactivation,virulence,immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2400
Faculty \ School:	Faculty of Science > School of Pharmacy
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	14 Jul 2020 23:51
Last Modified:	22 Oct 2022 06:29
URI:	https://ueaeprints.uea.ac.uk/id/eprint/76074
DOI:	10.2174/1874285801307010034

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