Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent

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dc.contributor.authorThangamani, Shankaren
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorAbushahba, Mostafa FN N.en
dc.contributor.authorHamed, Maha I.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.accessioned2020-09-21T16:15:43Zen
dc.date.available2020-09-21T16:15:43Zen
dc.date.issued2015-11-10en
dc.date.updated2020-09-21T16:15:41Zen
dc.description.abstractThe rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad-spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin's ability to suppress production of key MRSA toxins (α-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 16407 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/srep16407en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.othersrep16407 (PII)en
dc.identifier.pmid26553420 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100038en
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.subjectRESISTANT STAPHYLOCOCCUS-AUREUSen
dc.subjectCOA REDUCTASE INHIBITORSen
dc.subjectCOENZYME-A REDUCTASEen
dc.subjectMACROMOLECULAR-SYNTHESISen
dc.subjectANTIMICROBIAL PEPTIDESen
dc.subjectSTATINSen
dc.subjectANTIBIOTICSen
dc.subjectEXPRESSIONen
dc.subjectVIRULENCEen
dc.subjectTHERAPYen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshBiofilmsen
dc.subject.meshGram-Negative Bacteriaen
dc.subject.meshStaphylococcusen
dc.subject.meshStaphylococcal Skin Infectionsen
dc.subject.meshDisease Models, Animalen
dc.subject.meshSimvastatinen
dc.subject.meshInflammation Mediatorsen
dc.subject.meshCytokinesen
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitorsen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshAdministration, Topicalen
dc.subject.meshDrug Synergismen
dc.subject.meshFemaleen
dc.subject.meshMetabolic Networks and Pathwaysen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.subject.meshHypolipidemic Agentsen
dc.subject.meshProteolysisen
dc.titleExploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agenten
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2015-10-13en
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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