Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus

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dc.contributor.authorMohammad, Haroonen
dc.contributor.authorYounis, Waleeden
dc.contributor.authorEzzat, Hany G.en
dc.contributor.authorPeters, Christine E.en
dc.contributor.authorAbdelKhalek, Ahmeden
dc.contributor.authorCooper, Bruceen
dc.contributor.authorPogliano, Kiten
dc.contributor.authorPogliano, Joeen
dc.contributor.authorMayhoub, Abdelrahman S.en
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:17:04Zen
dc.date.available2020-09-21T16:17:04Zen
dc.date.issued2017-08-10en
dc.date.updated2020-09-21T16:17:00Zen
dc.description.abstractBacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents.en
dc.description.versionPublished versionen
dc.format.extent20 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e0182821 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0182821en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.otherPONE-D-17-23950 (PII)en
dc.identifier.pmid28797064 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100041en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherPLoSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPANTON-VALENTINE LEUKOCIDINen
dc.subjectCOMMUNITY-ASSOCIATED MRSAen
dc.subjectCELL-WALL SYNTHESISen
dc.subjectIN-VITROen
dc.subjectPSEUDOMONAS-AERUGINOSAen
dc.subjectBACILLUS-SUBTILISen
dc.subjectANTIBACTERIALen
dc.subjectVANCOMYCINen
dc.subjectINFECTIONSen
dc.subjectBINDINGen
dc.subject.meshHumansen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshCarbanilidesen
dc.subject.meshMethicillinen
dc.subject.meshVancomycinen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshMethicillin Resistanceen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.titleBacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureusen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2017-07-25en
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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