A protein that activates expression of a multidrug efflux transporter upon binding the transporter substrates.

Ahmed, Maqbool; Borsch, C M; Taylor, S. S.; Vázquez‐Laslop, Nora; Neyfakh, Alexander A.

doi:10.1016/s0021-9258(18)46956-6

Cited by 175 publications

(27 citation statements)

References 30 publications

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“…All K D determinations take into account ligand saturation and quenching. The fluorescence-based K D values determined for 1 and 4 reproduce previously reported values determined by other methods. ,, …”

Section: Resultssupporting

confidence: 85%

“…The fluorescence-based K D values determined for 1 and 4 reproduce previously reported values determined by other methods. 20,32,37 To determine if the quenching-based K D values reflect binding specifically at the putative effector-pocket, we also employed a competitive, anisotropy-based method in which RH6G-1, the known inducer, is displaced from BmrR by different ligands. 42 As expected, the anisotropy of the 1 emission decreases with increasing concentrations of competing ligands.…”

Section: ■ Resultsmentioning

confidence: 99%

“…BmrR is a MDR regulator from Bacillus subtilis that is widely regarded as a bacterial prototype for investigating MD recognition (Figure ). , It also controls the expression of the Bmr efflux pump in response to unrelated lipophilic cations and other compounds. , In contrast to canonical views of MDR functions, BmrR supports MD binding in a small, rigid pocket. To date, investigations of ligand interactions in the noncanonical BmrR pocket have utilized a battery of approaches, including chemical probes.…”

Section: Introductionmentioning

confidence: 99%

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Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR

Gunio

Froehlig

Pappas

et al. 2016

J. Chem. Inf. Model.

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Solution-binding and molecular docking have been combined with a diverse collection of chemical probes to further elucidate multidrug (MD) recognition in BmrR. Whereas previous efforts have focused on structural elucidations of MD binding, the present study examines features imparted by structure, including the recognition properties of the ligand-pocket, ligand structural requirements, and key factors that define and influence binding. Whereas MD-pockets are generally believed to be featureless and very hydrophobic, log KD-clog P correlations observed for BmrR and other polyspecific proteins suggest polar contributions are required for broad-spectrum recognition of amphipathic ligands. We show that molecular docking simulations recapitulate key features of MD recognition and have been employed to further inform contributions from structure. In addition to elaborating our understanding of the structures and functional roles of pocket elements that dictate broad-spectrum binding, molecular docking has implication additional features that likely play major roles, including ligand dynamics and multiple ligand-binding modes.

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Section: Resultssupporting

confidence: 85%

Section: ■ Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR

Gunio

Froehlig

Pappas

et al. 2016

J. Chem. Inf. Model.

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“…The activities of many regulators of the efflux pumps are frequently affected by the substrates that will be transported by the regulated efflux pump [166][167][168][169][170]. These regulators usually contain a drug-binding pocket within the ligand-binding domain, and the binding of the drug to these regulators modulates their transcriptional repressor/activator activities [171][172][173][174].…”

Section: Inducible Efflux Pumpsmentioning

confidence: 99%

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Sionov

Steinberg

2022

Microorganisms

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Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that are composed of mono- or multi-species cultures of bacteria/fungi embedded in an extracellular matrix produced by the microorganisms. Biofilm formation is, among others, regulated by quorum sensing (QS) which is an interbacterial communication system usually composed of two-component systems (TCSs) of secreted autoinducer compounds that activate signal transduction pathways through interaction with their respective receptors. Embedded in the biofilms, the bacteria are protected from environmental stress stimuli, and they often show reduced responses to antibiotics, making it difficult to eradicate the bacterial infection. Besides reduced penetration of antibiotics through the intricate structure of the biofilms, the sessile biofilm-embedded bacteria show reduced metabolic activity making them intrinsically less sensitive to antibiotics. Moreover, they frequently express elevated levels of efflux pumps that extrude antibiotics, thereby reducing their intracellular levels. Some efflux pumps are involved in the secretion of QS compounds and biofilm-related materials, besides being important for removing toxic substances from the bacteria. Some efflux pump inhibitors (EPIs) have been shown to both prevent biofilm formation and sensitize the bacteria to antibiotics, suggesting a relationship between these processes. Additionally, QS inhibitors or quenchers may affect antibiotic susceptibility. Thus, targeting elements that regulate QS and biofilm formation might be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.

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“…The first evidence against the sloppy translocase model came from the finding by Ahmed et al [8] of a transcriptional activator that controls the expression of the Bmr multidrug pump in a gram-positive Bacillus subtilis. Antimicrobial substrates of the Bmr pump, such as rhodamine or tetraphenyl phosphonium, induce the expression of the gene encoding the pump protein (Figure 1).…”

mentioning

confidence: 99%

Multidrug resistance: Versatile drug sensors of bacterial cells

Lewis

1999

Current Biology

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A protein that activates expression of a multidrug efflux transporter upon binding the transporter substrates.

Cited by 175 publications

References 30 publications

Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR

Solution-Binding and Molecular Docking Approaches Combine to Provide an Expanded View of Multidrug Recognition in the MDR Gene Regulator BmrR

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Multidrug resistance: Versatile drug sensors of bacterial cells

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