Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model

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dc.contributor.authorMohammad, Haroonen
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:17:31Zen
dc.date.available2020-09-21T16:17:31Zen
dc.date.issued2020-04-29en
dc.date.updated2020-09-21T16:17:27Zen
dc.description.abstractPressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin’s in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (107 CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log10 reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log10 reduction) and oral clindamycin (1.24-log10 reduction), which are used to treat infected PUs clinically. The present study highlights auranofin’s potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.en
dc.description.versionPublished versionen
dc.format.extent8 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 7251 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-020-64352-2en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-020-64352-2 (PII)en
dc.identifier.pmid32350417 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100043en
dc.identifier.volume10en
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.subjectSKINen
dc.subjectRETAPAMULINen
dc.subjectSELECTIONen
dc.subjectSURFACEen
dc.subjectINJURYen
dc.titleAuranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Modelen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-04-14en
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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