Repurposing celecoxib as a topical antimicrobial agent

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dc.contributor.authorThangamani, Shankaren
dc.contributor.authorYounis, Waleeden
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:12:25Zen
dc.date.available2020-09-21T16:12:25Zen
dc.date.issued2015-07-28en
dc.date.updated2020-09-21T16:12:21Zen
dc.description.abstractThere is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-a, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections.en
dc.description.versionPublished versionen
dc.format.extent12 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fmicb.2015.00750en
dc.identifier.eissn1664-302Xen
dc.identifier.issn1664-302Xen
dc.identifier.issueJULen
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.pmid26284040 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100026en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMicrobiologyen
dc.subjectcelecoxiben
dc.subjectantimicrobial resistanceen
dc.subjectrepurposingen
dc.subjectskin infectionen
dc.subjectanti-inflammatoryen
dc.subjectRESISTANT STAPHYLOCOCCUS-AUREUSen
dc.subjectCOMMUNITY-ASSOCIATED STRAINSen
dc.subjectFUSIDIC ACID RESISTANCEen
dc.subjectCYCLOOXYGENASE-2 INHIBITORen
dc.subjectPSEUDOMONAS-AERUGINOSAen
dc.subjectESCHERICHIA-COLIen
dc.subjectINFLAMMATIONen
dc.subjectINFECTIONSen
dc.subjectEPIDEMIOLOGYen
dc.subjectARTHRITISen
dc.subject0502 Environmental Science and Managementen
dc.subject0503 Soil Sciencesen
dc.subject0605 Microbiologyen
dc.titleRepurposing celecoxib as a topical antimicrobial agenten
dc.title.serialFrontiers in Microbiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2015-07-08en
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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