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Repurposing bioactive aporphine alkaloids as efflux pump inhibitors

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dc.contributor.authorSARIYAR AKBULUT, BERNA
dc.contributor.authorsAvci, Fatma Gizem; Atas, Basak; Aksoy, Cemile Selin; Kurpejovic, Eldin; Toplan, Gizem Gulsoy; Gurer, Caglayan; Guillerminet, Maxime; Orelle, Cedric; Jault, Jean-Michel; Akbulut, Berna Sariyar
dc.date.accessioned2022-03-14T09:06:31Z
dc.date.available2022-03-14T09:06:31Z
dc.date.issued2019-11
dc.description.abstractExtrusion of drugs or drug-like compounds through bacterial efflux pumps is a serious health issue that leads to loss in drug efficacy. Combinatorial therapies of low-efficacy drugs with efflux pump inhibitors may help to restore the activities of such drugs. In this quest, natural products are attractive molecules, since in addition to their wide range of bioactivities they may inhibit efflux pumps. The current work repurposed the bioactive alkaloid roemerine as a potential efflux pump inhibitor. In Bacillus subtilis, both Bmr and BmrA, belonging to the major facilitator and the ATP-binding cassette superfamilies, respectively, were found to be inhibited by roemerine. Scanning electron microscopy and RNA-Seq analyses showed that it potentiated the effect of berberine. Growth rates and checkerboard assays confirmed the synergy of roemerine and berberine and that roemerine prevented berberine efflux by inhibiting Bmr. Transport assays with inverted membrane vesicles prepared from Escherichia cob overexpressing BmrA showed that increasing roemerine concentration decreased the transport of doxorubicin, the BmrA substrate, confirming that roemerine may also be considered as an inhibitor of BmrA. Thus, these findings suggest that conjugation of roemerine to substrates of efflux pumps, Bmr and BmrA, may help to potentiate the activity of their drug substrates.
dc.identifier.doi10.1016/j.fitote.2019.104371
dc.identifier.eissn1873-6971
dc.identifier.issn0367-326X
dc.identifier.pubmed31629051
dc.identifier.urihttps://hdl.handle.net/11424/242524
dc.identifier.wosWOS:000501622300020
dc.language.isoeng
dc.publisherELSEVIER
dc.relation.ispartofFITOTERAPIA
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEfflux pump inhibition
dc.subjectAlkaloid
dc.subjectRoemerine
dc.subjectBerberine
dc.subjectBmr
dc.subjectBmrA
dc.subjectMULTIDRUG-RESISTANT PHENOTYPE
dc.subjectBACILLUS-SUBTILIS
dc.subjectSTAPHYLOCOCCUS-AUREUS
dc.subjectESCHERICHIA-COLI
dc.subjectANTIBACTERIAL ACTIVITY
dc.subjectTRANSPORTER
dc.subjectBERBERINE
dc.subjectEXPRESSION
dc.subjectIDENTIFICATION
dc.subjectBINDING
dc.titleRepurposing bioactive aporphine alkaloids as efflux pump inhibitors
dc.typearticle
dspace.entity.typePublication
local.avesis.id54fafc5e-29e8-4116-8705-01cd6c80b9d1
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumber104371
local.journal.numberofpages8
local.journal.quartileQ3
oaire.citation.titleFITOTERAPIA
oaire.citation.volume139
relation.isAuthorOfPublicationa9f127d3-8332-44dd-a532-34f3ef20bdb5
relation.isAuthorOfPublication.latestForDiscoverya9f127d3-8332-44dd-a532-34f3ef20bdb5

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