Review

Inhibition of drug efflux pumps in Staphylococcus aureus: current status of potentiating existing antibiotics

Bryan D Schindler

John D Dingell Veterans Affairs Medical Center, Wayne State University, Detroit, MI 48201, USA

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Pauline Jacinto

School of Medicine, Wayne State University, Detroit, MI 48201, USA

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Glenn W Kaatz

* Author for correspondence

College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI 48201, USA. .

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Email the corresponding author at gkaatz@juno.com

Published Online:27 Mar 2013https://doi.org/10.2217/fmb.13.16

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Abstract

The emergence of multidrug-resistant Staphylococcus aureus coupled with a declining output of new antibiotic treatment options from the pharmaceutical industry is a growing worldwide healthcare problem. Multidrug efflux pumps are known to play a role in antibiotic and biocide resistance in S. aureus. These membrane transporters are capable of extruding drugs and other structurally unrelated compounds, hence decreasing intracellular concentration and increasing survival. Coadministration of efflux pump inhibitors (EPIs) with antibiotics that are pump substrates could increase intracellular drug levels, thus bringing renewed efficacy to existing antistaphylococcal agents. Numerous EPIs have been identified or synthesized over the past two decades; these include existing pharmacologic drugs, naturally occurring compounds, and synthetic derivatives thereof. This review describes the current progress in EPI development for use against S. aureus.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Financial & competing interests disclosure

Research in the laboratory of GW Kaatz is supported by Veterans Affairs Biomedical Laboratory Research and Development funds (grant no. 1IO1BX000465). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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