Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections

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dc.contributor.authorThangamani, Shankaren
dc.contributor.authorYounis, Waleeden
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:11:54Zen
dc.date.available2020-09-21T16:11:54Zen
dc.date.issued2015-06-26en
dc.date.updated2020-09-21T16:11:49Zen
dc.description.abstractNovel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 11596 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/srep11596en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.othersrep11596 (PII)en
dc.identifier.pmid26111644 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100024en
dc.identifier.volume5en
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.subjectSOFT-TISSUE INFECTIONSen
dc.subjectCA-MRSA SKINen
dc.subjectIN-VITROen
dc.subjectAUREUSen
dc.subjectANTIBIOTICSen
dc.subjectANTIOXIDANTen
dc.subjectINFLAMMATIONen
dc.subjectEXPRESSIONen
dc.subjectCOMPOUNDen
dc.subjectDRUGSen
dc.subject.meshCells, Cultureden
dc.subject.meshKeratinocytesen
dc.subject.meshSkinen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshHumansen
dc.subject.meshBiofilmsen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshOrganoselenium Compoundsen
dc.subject.meshAzolesen
dc.subject.meshDaptomycinen
dc.subject.meshMupirocinen
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidalen
dc.subject.meshBacterial Toxinsen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshMethicillin Resistanceen
dc.subject.meshCell Survivalen
dc.subject.meshDrug Synergismen
dc.subject.meshFemaleen
dc.subject.meshHost-Pathogen Interactionsen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.subject.meshDrug Repositioningen
dc.titleRepurposing ebselen for treatment of multidrug-resistant staphylococcal infectionsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2015-05-21en
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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