Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model

Simple item page
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorCushman, Marken
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:17:58Zen
dc.date.available2020-09-21T16:17:58Zen
dc.date.issued2015-11-04en
dc.date.updated2020-09-21T16:17:56Zen
dc.description.abstractThe emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e0142321 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0142321en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue11en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.otherPONE-D-15-22389 (PII)en
dc.identifier.pmid26536129 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100045en
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.subjectMUPIROCIN RESISTANCEen
dc.subjectVANCOMYCINen
dc.subjectANTIBIOTICSen
dc.subjectCOMBINATIONen
dc.subjectEPIDEMIOLOGYen
dc.subjectCLINDAMYCINen
dc.subjectAMOXICILLINen
dc.subjectCLAVULANATEen
dc.subjectEMERGENCEen
dc.subjectGENESen
dc.subject.meshKeratinocytesen
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshStaphylococcal Skin Infectionsen
dc.subject.meshThiazolesen
dc.subject.meshMupirocinen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshAdministration, Topicalen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.titleAntibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Modelen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2015-10-19en
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

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aure.pdf
Size:
306.11 KB
Format:
Adobe Portable Document Format
Download

Collections

All Faculty Deposits
Scholarly Works, Biomedical Sciences and Pathobiology