Repurposing ebselen for decolonization of vancomycin-resistant enterococci (VRE)

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dc.contributor.authorAbdelKhalek, Ahmeden
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:11:32Zen
dc.date.available2020-09-21T16:11:32Zen
dc.date.issued2018-06-28en
dc.date.updated2020-09-21T16:11:28Zen
dc.description.abstractEnterococci represent one of the microbial world’s most challenging enigmas. Colonization of the gastrointestinal tract (GIT) of high-risk/immunocompromised patients by enterococci exhibiting resistance to vancomycin (VRE) can lead to life-threating infections, including bloodstream infections and endocarditis. Decolonization of VRE from the GIT of high-risk patients represents an alternative method to suppress the risk of the infection. It could be considered as a preventative measure to protect against VRE infections in high-risk individuals. Though multiple agents (ramoplanin and bacitracin) have been evaluated clinically, no drugs are currently approved for use in VRE decolonization of the GIT. The present study evaluates ebselen, a clinical molecule, for use as a decolonizing agent against VRE. When evaluated against a broad array of enterococcal isolates in vitro, ebselen was found to be as potent as linezolid (minimum inhibitory concentration against 90% of clinical isolates tested was 2 μg/ml). Though VRE has a remarkable ability to develop resistance to antibacterial agents, no resistance to ebselen emerged after a clinical isolate of vancomycin-resistant E. faecium was serially-passaged with ebselen for 14 days. Against VRE biofilm, a virulence factor that enables the bacteria to colonize the gut, ebselen demonstrated the ability to both inhibit biofilm formation and disrupt mature biofilm. Furthermore, in a murine VRE colonization reduction model, ebselen proved as effective as ramoplanin in reducing the bacterial shedding and burden of VRE present in the fecal content (by > 99.99%), cecum, and ileum of mice. Based on the promising results obtained, ebselen warrants further investigation as a novel decolonizing agent to quell VRE infection.en
dc.description.versionPublished versionen
dc.format.extent14 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e0199710 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0199710en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue6en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.otherPONE-D-18-09775 (PII)en
dc.identifier.pmid29953486 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100023en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherPLoSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectINDUCED HEARING-LOSSen
dc.subjectQUINUPRISTIN-DALFOPRISTINen
dc.subjectSTAPHYLOCOCCAL INFECTIONSen
dc.subjectCLOSTRIDIUM-DIFFICILEen
dc.subjectCOLONIZED PATIENTSen
dc.subjectDOUBLE-BLINDen
dc.subjectFAECIUMen
dc.subjectMECHANISMSen
dc.subjectMANAGEMENTen
dc.subjectEMERGENCEen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshBiofilmsen
dc.subject.meshEnterococcus faeciumen
dc.subject.meshGram-Positive Bacterial Infectionsen
dc.subject.meshOrganoselenium Compoundsen
dc.subject.meshAzolesen
dc.subject.meshVirulence Factorsen
dc.subject.meshVancomycin Resistanceen
dc.subject.meshFemaleen
dc.titleRepurposing ebselen for decolonization of vancomycin-resistant enterococci (VRE)en
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2018-06-12en
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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