Antimicrobial Efflux Pumps

Varela, Manuel F.

doi:10.1002/9781119282549.ch8

Cited by 4 publications

(3 citation statements)

References 88 publications

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“…In particular, multidrug efflux pumps serve to provide active resistance to a constellation of otherwise potentially useful antimicrobial agents by actively exporting the agents from the intracellular location of bacteria to the extracellular milieu, where such agents are ineffective [7]. Several large superfamilies of transporters contain many thousands of constituents, many of which are devoted to Microorganisms 2020, 8, 266; doi:10.3390/microorganisms8020266 www.mdpi.com/journal/microorganisms the extrusion of anti-bacterial drugs [8].…”

Section: Introductionmentioning

confidence: 99%

Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps

et al. 2020

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Pathogenic microorganisms that are multidrug-resistant can pose severe clinical and public health concerns. In particular, bacterial multidrug efflux transporters of the major facilitator superfamily constitute a notable group of drug resistance mechanisms primarily because multidrug-resistant pathogens can become refractory to antimicrobial agents, thus resulting in potentially untreatable bacterial infections. The major facilitator superfamily is composed of thousands of solute transporters that are related in terms of their phylogenetic relationships, primary amino acid sequences, two- and three-dimensional structures, modes of energization (passive and secondary active), and in their mechanisms of solute and ion translocation across the membrane. The major facilitator superfamily is also composed of numerous families and sub-families of homologous transporters that are conserved across all living taxa, from bacteria to humans. Members of this superfamily share several classes of highly conserved amino acid sequence motifs that play essential mechanistic roles during transport. The structural and functional importance of multidrug efflux pumps that belong to the major facilitator family and that are harbored by Gram-negative and -positive bacterial pathogens are considered here.

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Section: Introductionmentioning

confidence: 99%

Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps

et al. 2020

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“…The critical role of bacterial efflux pumps in antibiotic resistance has directed research efforts into identifying novel EPIs that can be used alongside antibiotics in clinical settings [28,29]. EPIs have been identified against the multidrug resistance (MDR) efflux pumps of most of the clinically relevant and most extensively studied pathogens.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel inhibitors of the ABC transporter BmrA

Serçinoğlu

Senturk

Kaya

et al. 2020

Bioorganic Chemistry

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The resistance of microbes to commonly used antibiotics has become a worldwide health problem. A major underlying mechanism of microbial antibiotic resistance is the export of drugs from bacterial cells. Drug efflux is mediated through the action of multidrug resistance efflux pumps located in the bacterial cell membranes. The critical role of bacterial efflux pumps in antibiotic resistance has directed research efforts to the identification of novel efflux pump inhibitors that can be used alongside antibiotics in clinical settings.Here, we aimed to find potential inhibitors of the archetypical ATP-binding cassette (ABC) efflux pump BmrA of Bacillus subtilis via virtual screening of the Mu.Ta.Lig. Chemotheca small molecule library.Molecular docking calculations targeting the nucleotide-binding domain of BmrA were performed using AutoDock Vina. Following a further drug-likeness filtering step , top 25 scorers were identified. These ligands were then clustered into separate groups based on their contact patterns with the BmrA nucleotide-binding domain. Six ligands with distinct contact patterns were used for further in vitro inhibition assays based on intracellular ethidium bromide accumulation. Using this methodology, we identified two novel inhibitors of BmrA from the Chemotheca small molecule library.

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“…Secondary active transporters also confer bacterial resistance to many structurally distinctive antimicrobial agents [ 115 , 116 ]. Throughout the last 30 years, these active antimicrobial efflux pump systems have been categorized into several large superfamilies of related proteins based on similarities in amino acid sequences, structures, and modes of energization [ 117 , 118 ]. Currently, these superfamilies are denoted as follows: the major facilitator superfamily (MFS) [ 119 ]; the drug/metabolite transporter (DMT) superfamily, which now harbors the small multidrug resistance (SMR) family [ 120 , 121 ]; the multidrug and toxic compound extrusion (MATE) family, which has been included within the larger multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily of transporters [ 122 , 123 ]; the proteobacterial antimicrobial compound efflux (PACE) transporter superfamily [ 124 ]; and the resistance-nodulation-cell division (RND) superfamily [ 125 ].…”

Section: Active Efflux Pumps Of Antimicrobial Agentsmentioning

confidence: 99%

Bacterial Resistance to Antimicrobial Agents

et al. 2021

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Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.

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Antimicrobial Efflux Pumps

Cited by 4 publications

References 88 publications

Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps

Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps

Identification of novel inhibitors of the ABC transporter BmrA

Bacterial Resistance to Antimicrobial Agents

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