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Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens

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dc.contributor.authorThangamani, Shankaren
dc.contributor.authorYounis, Waleeden
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:12:09Zen
dc.date.available2020-09-21T16:12:09Zen
dc.date.issued2015-07-29en
dc.date.updated2020-09-21T16:12:06Zen
dc.description.abstractWithout a doubt, our current antimicrobials are losing the battle in the fight against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet need for novel antimicrobials and novel approaches to develop them; however, it is becoming increasingly difficult and costly to develop new antimicrobials. One strategy to reduce the time and cost associated with antimicrobial innovation is drug repurposing, which is to find new applications outside the scope of the original medical indication of the drug. Ebselen, an organoselenium clinical molecule, possesses potent antimicrobial activity against clinical multidrug-resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of ebselen against Gram-positive pathogens exceeded those activities determined for vancomycin and linezolid, drugs of choice for treatment of Enterococcus and Staphylococcus infections. The minimum inhibitory concentrations of ebselen at which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed significant clearance of intracellular methicillinresistant S. aureus (MRSA) in comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the bacterial translation process without affecting mitochondrial biogenesis. Additionally, ebselen was found to exhibit excellent activity in vivo in a Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed synergistic activities with conventional antimicrobials against MRSA. Taken together, our results demonstrate that ebselen, with its potent antimicrobial activity and safety profiles, can be potentially used to treat multidrug resistant Gram-positive bacterial infections alone or in combination with other antibiotics and should be further clinically evaluated.en
dc.description.versionPublished versionen
dc.format.extent16 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e0133877 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0133877en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue7en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.otherPONE-D-15-20653 (PII)en
dc.identifier.pmid26222252 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100025en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherPLoSen
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.subjectINHIBITIONen
dc.subjectVANCOMYCINen
dc.subjectMECHANISMen
dc.subjectGENESen
dc.subjectANTIMICROBIALSen
dc.subjectCOMBINATIONen
dc.subjectEXPRESSIONen
dc.subjectBACTERIAen
dc.subject.meshCell Lineen
dc.subject.meshIntracellular Spaceen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshCaenorhabditis elegansen
dc.subject.meshGram-Positive Bacteriaen
dc.subject.meshOrganoselenium Compoundsen
dc.subject.meshAzolesen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshDrug Resistance, Bacterialen
dc.subject.meshDrug Resistance, Multipleen
dc.subject.meshProtein Biosynthesisen
dc.subject.meshTranscription, Geneticen
dc.subject.meshDrug Synergismen
dc.subject.meshDrug Repositioningen
dc.subject.meshOrganelle Biogenesisen
dc.titleRepurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogensen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2015-07-03en
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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