Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation
Christina Kourtesi,Anthony R. Ball,Ying-Ying Huang,Sanjay M Jachak,D Mariano A Vera,Proma Khondkar,Simon Gibbons,Michael R. Hamblin,George P. Tegos +8 more
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TLDR
Advances in the path of EPI discovery are summarized, potential avenues of E PI implementation and development are discussed, and the need for highly informative and comprehensive translational approaches is underlined.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.read more
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An overview of the antimicrobial resistance mechanisms of bacteria
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The value of antimicrobial peptides in the age of resistance
Maria Magana,Muthuirulan Pushpanathan,Ana L. Santos,Leon G. Leanse,Michael Fernandez,Anastasios Ioannidis,Marc A. Giulianotti,Yiorgos Apidianakis,Steven B. Bradfute,Andrew L. Ferguson,Artem Cherkasov,Mohamed N. Seleem,Clemencia Pinilla,Cesar de la Fuente-Nunez,Themis Lazaridis,Themis Lazaridis,Tianhong Dai,Richard A. Houghten,Robert E. W. Hancock,George P. Tegos +19 more
TL;DR: The benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens are identified, advances in the deployment of novel promising antimacterial peptides are highlighted, and the needs and priorities in designing focused development strategies taking into account the most advanced tools available are underlined.
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Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives
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Michael R. Hamblin,Tayyaba Hasan +1 more
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