Efflux Pumps of the Resistance–Nodulation–Division Family: A Perspective of their Structure, Function, and Regulation in Gram‐Negative Bacteria

Routh, Mathew D.; Zalucki, Yaramah M.; Su, Chih‐Chia; Long, Feng; Zhang, Qijing; Shafer, William M.; Yu, Edward

doi:10.1002/9780470920541.ch3

Cited by 42 publications

(40 citation statements)

References 141 publications

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“…Bacteria use specialized membrane-associated proteins to expel a wide range of compounds from the cytoplasm (11). Combined with reduced influx of these compounds and/or enzymatic degradation, efflux pumps are responsible for keeping the cytoplasmic concentrations of certain antimicrobial compounds below a critical threshold (11,12).…”

Section: The Role Of Efflux In Biofilm Resistancementioning

confidence: 99%

“…Combined with reduced influx of these compounds and/or enzymatic degradation, efflux pumps are responsible for keeping the cytoplasmic concentrations of certain antimicrobial compounds below a critical threshold (11,12). Bacterial efflux pumps can be divided into several superfamilies, with members of the RND family being the most studied when it comes to their involvement in bacterial biofilm resistance and/or biofilm formation.…”

Section: The Role Of Efflux In Biofilm Resistancementioning

confidence: 99%

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The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

Acker

Coenye

2016

Journal of Biological Chemistry

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Microbial biofilms demonstrate a decreased susceptibility to antimicrobial agents. Various mechanisms have been proposed to be involved in this recalcitrance. We focus on two of these factors. Firstly, the ability of sessile cells to actively mediate efflux of antimicrobial compounds has a profound impact on resistance and tolerance, and several studies point to the existence of biofilm-specific efflux systems. Secondly, biofilm-specific stress responses have a marked influence on cellular physiology, and contribute to the occurrence of persister cells. We provide an overview of the data that demonstrate that both processes are important for survival following exposure to antimicrobial agents.Microbial biofilms are surface-attached communities, consisting of cells embedded in an extracellular polymeric matrix that is at least partially composed of polymers produced by the microorganism themselves (1). Biofilms are omnipresent in natural and man-made environments (1, 2), and biofilm-associated bacteria are involved in a wide range of infections, including respiratory tract infections in cystic fibrosis (CF) 2 patients, chronically infected wounds, and device-related infections (3, 4). One of the hallmarks of these biofilm-associated infections is the frequent failure of antimicrobial chemotherapy. Although it is often postulated that sessile cells are more resistant to antimicrobial agents, these cells typically do not grow better than planktonic cells in the presence of antibiotics; for example, biofilm-associated and stationary-phase planktonic Burkholderia cepacia complex bacteria showed similar susceptibilities to antibiotics (5). However, it is much more difficult to kill biofilm-associated cells than planktonic cells (6), and various mechanisms that potentially could be involved in this have been described in the literature (see Refs. 7 and 8 for recent reviews as well as Refs. 9 and 10 in this minireview series). Avoiding exposure to (sufficiently high concentrations of) antibiotics, and the presence of a small population of specialized survivor cells that are tolerant toward particular antimicrobial agents (i.e. they are not killed upon exposure to the product) are two important mechanisms that will be discussed in this review.

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Section: The Role Of Efflux In Biofilm Resistancementioning

confidence: 99%

Section: The Role Of Efflux In Biofilm Resistancementioning

confidence: 99%

The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

Acker

Coenye

2016

Journal of Biological Chemistry

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“…It is widely accepted that the increased use of these drugs has resulted in bacteria that are adapted and more resistant to the typical treatments. Until recently, the major means of antimicrobial resistance in bacteria was believed to be similar to the breakdown of penicillin by β-lactamase, i.e., modification of the offending compound by a drug-specific enzyme (57, 101). However, as antibiotic engineering advances, so too do the methods of resistance.…”

Section: Multi-drug Resistance In Bacteriamentioning

confidence: 99%

“…However, as antibiotic engineering advances, so too do the methods of resistance. Currently, there are three major mechanisms bacteria use to avoid the toxic effects of biocides (84, 101, 106). …”

Section: Multi-drug Resistance In Bacteriamentioning

confidence: 99%

Bacterial Multidrug Efflux Transporters

Delmar¹,

Su²,

2014

Annu. Rev. Biophys.

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153

132

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Infections caused by bacteria remain a leading cause of death worldwide. While antibiotics remain a key clinical therapy, their effectiveness has been severely compromised by the development of drug resistance in these pathogens. A common and powerful resistance mechanism, multi-drug efflux transporters are capable of extruding a number of structurally unrelated antimicrobials from the bacterial cell, including antibiotics and toxic heavy metal ions, facilitating their survival in noxious environments. Those transporters belonging to the resistance-nodulation-cell division (RND) superfamily typically assemble as tripartite efflux complexes, spanning the inner and outer membranes of the cell envelope. In Escherichia coli, the CusCFBA complex, which mediates resistance to copper(I) and silver(I) ions, is the only known RND transporter with a specificity for heavy metals. Herein, we describe the current knowledge of individual pump components of the Cus system, a paradigm for efflux machinery, and speculate on how RND pumps assemble to fight diverse antimicrobials.

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“…Efflux pumps are plasma membrane-based units that recognise and extrude noxious substances such as antibiotics before they reach their intended targets and have been shown to be present in all bacteria [56][57][58][59][60][61], including mycobacteria [62][63][64][65][66][67][68]. When these efflux pumps are overexpressed, resistance to two or more antibiotics (multidrug resistance) occurs, and therapy of MDR infections is now problematic [69][70][71][72][73].…”

Section: The Role Of Overexpressed Efflux Pumps In Multidrug-resistanmentioning

confidence: 99%

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Amaral

Viveiros

2012

International Journal of Antimicrobial Agents

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Efflux Pumps of the Resistance–Nodulation–Division Family: A Perspective of their Structure, Function, and Regulation in Gram‐Negative Bacteria

Cited by 42 publications

References 141 publications

The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

The Role of Efflux and Physiological Adaptation in Biofilm Tolerance and Resistance

Bacterial Multidrug Efflux Transporters

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

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