The role played by drug efflux pumps in bacterial multidrug resistance

2017 ◽  
Vol 61 (1) ◽  
pp. 127-139 ◽  
Author(s):  
Mohsen Chitsaz ◽  
Melissa H. Brown
Keyword(s):  
Protein Sequence ◽  
Efflux Pumps ◽  
Mechanisms Of Action ◽  
Transport Proteins ◽  
Drug Efflux ◽  
Toxic Compounds ◽  
Membrane Transport Proteins ◽  
Protein Sequence Homology ◽  
Drug Efflux Pumps ◽  
A Current

Antimicrobial resistance is a current major challenge in chemotherapy and infection control. The ability of bacterial and eukaryotic cells to recognize and pump toxic compounds from within the cell to the environment before they reach their targets is one of the important mechanisms contributing to this phenomenon. Drug efflux pumps are membrane transport proteins that require energy to export substrates and can be selective for a specific drug or poly-specific that can export multiple structurally diverse drug compounds. These proteins can be classified into seven groups based on protein sequence homology, energy source and overall structure. Extensive studies on efflux proteins have resulted in a wealth of knowledge that has made possible in-depth understanding of the structures and mechanisms of action, substrate profiles, regulation and possible inhibition of many clinically important efflux pumps. This review focuses on describing known families of drug efflux pumps using examples that are well characterized structurally and/or biochemically.

The Role of NIR Fluorescence in MDR Cancer Treatment: From Targeted Imaging to Phototherapy

2020 ◽  
Vol 27 (33) ◽  
pp. 5510-5529
Author(s):  
Zengtao Wang ◽  
Qingqing Meng ◽  
Shaoshun Li
Keyword(s):  
Cancer Treatment ◽  
Near Infrared ◽  
Combined Therapy ◽  
Efflux Pumps ◽  
Cross Resistance ◽  
Great Promise ◽  
Drug Efflux ◽  
Nir Dyes ◽  
Nir Imaging ◽  
Drug Efflux Pumps

Background: Multidrug Resistance (MDR) is defined as a cross-resistance of cancer cells to various chemotherapeutics and has been demonstrated to correlate with drug efflux pumps. Visualization of drug efflux pumps is useful to pre-select patients who may be insensitive to chemotherapy, thus preventing patients from unnecessary treatment. Near-Infrared (NIR) imaging is an attractive approach to monitoring MDR due to its low tissue autofluorescence and deep tissue penetration. Molecular NIR imaging of MDR cancers requires stable probes targeting biomarkers with high specificity and affinity. Objective: This article aims to provide a concise review of novel NIR probes and their applications in MDR cancer treatment. Results: Recently, extensive research has been performed to develop novel NIR probes and several strategies display great promise. These strategies include chemical conjugation between NIR dyes and ligands targeting MDR-associated biomarkers, native NIR dyes with inherent targeting ability, activatable NIR probes as well as NIR dyes loaded nanoparticles. Moreover, NIR probes have been widely employed for photothermal and photodynamic therapy in cancer treatment, which combine with other modalities to overcome MDR. With the rapid advancing of nanotechnology, various nanoparticles are incorporated with NIR dyes to provide multifunctional platforms for controlled drug delivery and combined therapy to combat MDR. The construction of these probes for MDR cancers targeted NIR imaging and phototherapy will be discussed. Multimodal nanoscale platform which integrates MDR monitoring and combined therapy will also be encompassed. Conclusion: We believe these NIR probes project a promising approach for diagnosis and therapy of MDR cancers, thus holding great potential to reach clinical settings in cancer treatment.

scholarly journals Interdependence of multi-drug efflux pumps and quorum sensing systems in Pseudomonas aeruginosa

2014 ◽  
Vol 21 ◽  
pp. 92
Author(s):  
K. Ganguly ◽  
J.L. Phillips ◽  
M.S. Wren ◽  
P.E. Pardington ◽  
S. Gnanakaran ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Efflux Pumps ◽  
Drug Efflux ◽  
Sensing Systems ◽  
Drug Efflux Pumps

The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood–testis barrier and in primary testicular tumours

2004 ◽  
Vol 40 (14) ◽  
pp. 2064-2070 ◽  
Author(s):  
J. Bart ◽  
H. Hollema ◽  
H.J.M. Groen ◽  
E.G.E. de Vries ◽  
N.H. Hendrikse ◽  
...  
Keyword(s):  
Efflux Pumps ◽  
Normal Blood ◽  
Drug Efflux ◽  
Testicular Tumours ◽  
Drug Efflux Pumps ◽  
Blood Testis Barrier

Antimicrobial Drug Efflux Pumps in Burkholderia

2016 ◽  
pp. 417-438 ◽  
Author(s):  
Viola Camilla Scoffone ◽  
Tom Coenye ◽  
Giovanna Riccardi ◽  
Silvia Buroni
Keyword(s):  
Efflux Pumps ◽  
Antimicrobial Drug ◽  
Drug Efflux ◽  
Drug Efflux Pumps

scholarly journals The Evolutionary Conservation of Escherichia coli Drug Efflux Pumps Supports Physiological Functions

2020 ◽  
Vol 202 (22) ◽  
Author(s):  
Tanisha Teelucksingh ◽  
Laura K. Thompson ◽  
Georgina Cox
Keyword(s):  
Escherichia Coli ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Evolutionary Conservation ◽  
Drug Efflux ◽  
Physiological Functions ◽  
Content Type ◽  
Bacterial Physiology ◽  
E Coli ◽  
Drug Efflux Pumps

ABSTRACT Bacteria harness an impressive repertoire of resistance mechanisms to evade the inhibitory action of antibiotics. One such mechanism involves efflux pump-mediated extrusion of drugs from the bacterial cell, which significantly contributes to multidrug resistance. Intriguingly, most drug efflux pumps are chromosomally encoded components of the intrinsic antibiotic resistome. In addition, in terms of xenobiotic detoxification, bacterial efflux systems often exhibit significant levels of functional redundancy. Efflux pumps are also considered to be highly conserved; however, the extent of conservation in many bacterial species has not been reported and the majority of genes that encode efflux pumps appear to be dispensable for growth. These observations, in combination with an increasing body of experimental evidence, imply alternative roles in bacterial physiology. Indeed, the ability of efflux pumps to facilitate antibiotic resistance could be a fortuitous by-product of ancient physiological functions. Using Escherichia coli as a model organism, we here evaluated the evolutionary conservation of drug efflux pumps and we provide phylogenetic analysis of the major efflux families. We show the E. coli drug efflux system has remained relatively stable and the majority (∼80%) of pumps are encoded in the core genome. This analysis further supports the importance of drug efflux pumps in E. coli physiology. In this review, we also provide an update on the roles of drug efflux pumps in the detoxification of endogenously synthesized substrates and pH homeostasis. Overall, gaining insight into drug efflux pump conservation, common evolutionary ancestors, and physiological functions could enable strategies to combat these intrinsic and ancient elements.

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