Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations.

By Jingjing Sun, Z. Deng, A. Yan. Biochemical and Biophysical Research Communications - BBRC, 2014

708 citations recorded by the source corpus.

Multidrug resistance (MDR) refers to the capability of bacterial pathogens to withstand lethal doses of structurally diverse drugs which are capable of eradicating non-resistant strains. MDR has been identified as a major threat to the public health of human being by the World Health Organization (WHO). Among the four general mechanisms that cause antibiotic resistance including target alteration, drug inactivation, decreased permeability and increased efflux, drug extrusion by the multidrug efflux pumps serves as an important mechanism of MDR. Efflux pumps not only can expel a broad range of antibiotics owing to their poly-substrate specificity, but also drive the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. Over-expression of multidrug efflux pumps have been increasingly found to be associated with clinically relevant drug resistance. On the other hand, accumulating evidence has suggested that efflux pumps also have physiological functions in bacteria and their expression is subject tight regulation in response to various of environmental and physiological signals. A comprehensive understanding of the mechanisms of drug extrusion, and regulation and physiological functions of efflux pumps is essential for the development of anti-resistance interventions. In this review, we summarize the development of these research areas in the recent decades and present the pharmacological exploitation of efflux pump inhibitors as a promising anti-drug resistance intervention.

Subfields: Molecular Biology, Molecular Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/bc1fe2146fc5d7df7571e742e67e223f4e6bd2e5

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Citations in the corpus

• Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens (2018, background): “In addition, many types of active efflux pumps have been described in Gram-positive and Gram-negative bacteria, which generally belong to one of the five families: ABC, MFS, RND (Resistance-Nodulation-Division), MATE (Multidrug and Toxin Extrusion), and SMR (Small Multidrug Resistance) (Sun et al., ”
• Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence (2017, background): “…resistance among P. aeruginosa isolates can be mediated by either mutational changes within the fluoroquinolone targets i.e., DNA gyrase (gyrA and gyrB) and/or topoisomerase IV (parC and parE) or overproduction of active or inducible efflux pumps (Lee et al., 2005; Sun et al., 2014; Figure 3).”