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Identification of novel inhibitors of the ABC transporter BmrA

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dc.contributor.authorSARIYAR AKBULUT, BERNA
dc.contributor.authorsSercinoglu, Onur; Senturk, Duygu; Kaya, Fatma Ece Altinisik; Avci, Fatma Gizem; Frlan, Rok; Tomasic, Tihomir; Ozbek, Pemra; Orelle, Cedric; Jault, Jean-Michel; Akbulut, Berna Sariyar
dc.date.accessioned2022-03-14T09:24:06Z
dc.date.available2022-03-14T09:24:06Z
dc.date.issued2020-12
dc.description.abstractThe 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 based on Lipinski's Rule of Five, 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.
dc.identifier.doi10.1016/j.bioorg.2020.104452
dc.identifier.eissn1090-2120
dc.identifier.issn0045-2068
dc.identifier.pubmed33212311
dc.identifier.urihttps://hdl.handle.net/11424/243072
dc.identifier.wosWOS:000603573500004
dc.language.isoeng
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE
dc.relation.ispartofBIOORGANIC CHEMISTRY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBmrA
dc.subjectEfflux pump inhibitors
dc.subjectAntibiotic resistance
dc.subjectNucleotide-binding domain
dc.subjectMolecular docking
dc.subjectVirtual screening
dc.subjectChemotheca
dc.subjectMULTIDRUG EFFLUX PUMP
dc.subjectP-GLYCOPROTEIN
dc.subjectBACILLUS-SUBTILIS
dc.subjectNUCLEOTIDE-BINDING
dc.subjectDRUG-RESISTANCE
dc.subjectATP-BINDING
dc.subjectIN-SILICO
dc.subjectSTAPHYLOCOCCUS-AUREUS
dc.subjectREVERSAL AGENTS
dc.subjectACRB
dc.titleIdentification of novel inhibitors of the ABC transporter BmrA
dc.typearticle
dspace.entity.typePublication
local.avesis.id2261d7b4-5473-4bfa-8a71-8614152cc91b
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumber104452
local.journal.numberofpages8
local.journal.quartileQ1
oaire.citation.titleBIOORGANIC CHEMISTRY
oaire.citation.volume105
relation.isAuthorOfPublicationa9f127d3-8332-44dd-a532-34f3ef20bdb5
relation.isAuthorOfPublication.latestForDiscoverya9f127d3-8332-44dd-a532-34f3ef20bdb5

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