Antibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogens

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dc.contributor.authorThangamani, Shankaren
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorAbushahba, Mostafa FN N.en
dc.contributor.authorSobreira, Tiago JP P.en
dc.contributor.authorHedrick, Victoria E.en
dc.contributor.authorPaul, Lake N.en
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:08:44Zen
dc.date.available2020-09-21T16:08:44Zen
dc.date.issued2016-03-03en
dc.date.updated2020-09-21T16:08:40Zen
dc.description.abstractTraditional methods employed to discover new antibiotics are both a time-consuming and financially-taxing venture. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). Such an effort led to the discovery of auranofin, a drug initially approved as an anti-rheumatic agent, which also possesses potent antibacterial activity in a clinically achievable range. The present study demonstrates auranofin's antibacterial activity is a complex process that involves inhibition of multiple biosynthetic pathways including cell wall, DNA, and bacterial protein synthesis. We also confirmed that the lack of activity of auranofin observed against Gram-negative bacteria is due to the permeability barrier conferred by the outer membrane. Auranofin's ability to suppress bacterial protein synthesis leads to significant reduction in the production of key methicillin-resistant Staphylococcus aureus (MRSA) toxins. Additionally, auranofin is capable of eradicating intracellular MRSA present inside infected macrophage cells. Furthermore, auranofin is efficacious in a mouse model of MRSA systemic infection and significantly reduces the bacterial load in murine organs including the spleen and liver. Collectively, this study provides valuable evidence that auranofin has significant promise to be repurposed as a novel antibacterial for treatment of invasive bacterial infections.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 22571 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/srep22571en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.othersrep22571 (PII)en
dc.identifier.pmid26936660 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100015en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectINTRACELLULAR STAPHYLOCOCCUS-AUREUSen
dc.subjectANTIBIOTIC-RESISTANCEen
dc.subjectESCHERICHIA-COLIen
dc.subjectNECROTIZING PNEUMONIAen
dc.subjectINFECTIONSen
dc.subjectDRUGen
dc.subjectSTRAINSen
dc.subjectEPIDEMIOLOGYen
dc.subjectMODELen
dc.subjectSUSCEPTIBILITYen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshAuranofinen
dc.subject.meshBacterial Proteinsen
dc.subject.meshDrug Resistance, Multiple, Bacterialen
dc.subject.meshProtein Biosynthesisen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.titleAntibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogensen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2016-02-17en
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Techen

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