Evaluation of ebselen in resolving a methicillin-resistant Staphylococcus aureus infection of pressure ulcers in obese and diabetic mice

Simple item page
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorDieterly, Alexandra M.en
dc.contributor.authorLyle, L. Tiffanyen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-05-13T12:03:58Zen
dc.date.available2021-05-13T12:03:58Zen
dc.date.issued2021-02-22en
dc.description.abstractPressure ulcers (PUs) are a source of morbidity in individuals with restricted mobility including individuals that are obese or diabetic. Infection of PUs with pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), impairs ulcers from healing. The present study evaluated ebselen as a topical antibacterial to treat MRSA-infected PUs. Against two different S. aureus strains, including MRSA USA300, resistance to ebselen did not emerge after 14 consecutive passages. Resistance to mupirocin emerged after only five passages. Additionally, ebselen was found to exert a modest postantibiotic effect of five hours against two MRSA strains. Ebselen was subsequently evaluated in MRSA-infected PUs in two models using obese and diabetic mice. In obese mice, topical ebselen (89.2% reduction) and oral linezolid (84.5% reduction) similarly reduced the burden of MRSA in infected PUs. However, in diabetic mice, topical ebselen (45.8% reduction in MRSA burden) was less effective. Histopathological evaluation of ulcers in diabetic mice determined that ebselen treatment resulted in fewer bacterial colonies deep within the dermis and that the treatment exhibited evidence of epithelial regeneration. Topical mupirocin was superior to ebselen in reducing MRSA burden in infected PUs both in obese (98.7% reduction) and diabetic (99.3% reduction) mice. Ebselen's antibacterial activity was negatively impacted as the bacterial inoculum was increased from 10(5) CFU/mL to 10(7) CFU/mL. These results suggest that a higher dose of ebselen, or a longer course of treatment, may be needed to achieve a similar effect as mupirocin in topically treating MRSA-infected pressure ulcers.en
dc.description.notesThis work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (URL: https://www.niaid.nih.gov/) awarded to MNS (grant number R01AI130186). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI130186]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0247508en
dc.identifier.issn1932-6203en
dc.identifier.issue2en
dc.identifier.othere0247508en
dc.identifier.pmid33617589en
dc.identifier.urihttp://hdl.handle.net/10919/103260en
dc.identifier.volume16en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleEvaluation of ebselen in resolving a methicillin-resistant Staphylococcus aureus infection of pressure ulcers in obese and diabetic miceen
dc.title.serialPlos Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
journal.pone.0247508.pdf
Size:
2.06 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Scholarly Works, Biomedical Sciences and Pathobiology
Destination Area: Global Systems Science (GSS)