A short D-enantiomeric antimicrobial peptide with potent immunomodulatory and antibiofilm activity against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii

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dc.contributor.authorMohamed, Mohamed F.en
dc.contributor.authorBrezden, Annaen
dc.contributor.authorMohammad, Haroonen
dc.contributor.authorChmielewski, Jeanen
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:08:06Zen
dc.date.available2020-09-21T16:08:06Zen
dc.date.issued2017-07-31en
dc.date.updated2020-09-21T16:08:00Zen
dc.description.abstractAntimicrobial peptides (AMPs) represent a promising therapeutic alternative for the treatment of antibiotic-resistant bacterial infections. The present study investigates the antimicrobial activity of new, rationally-designed derivatives of a short α-helical peptide, RR. From the peptides designed, RR4 and its D-enantiomer, D-RR4, emerged as the most potent analogues with a more than 32-fold improvement in antimicrobial activity observed against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Remarkably, D-RR4 demonstrated potent activity against colistin-resistant strains of P. aeruginosa (isolated from cystic fibrosis patients) indicating a potential therapeutic advantage of this peptide over several AMPs. In contrast to many natural AMPs, D-RR4 retained its activity under challenging physiological conditions (high salts, serum, and acidic pH). Furthermore, D-RR4 was more capable of disrupting P. aeruginosa and A. baumannii biofilms when compared to conventional antibiotics. Of note, D-RR4 was able to bind to lipopolysaccharide to reduce the endotoxin-induced proinflammatory cytokine response in macrophages. Finally, D-RR4 protected Caenorhabditis elegans from lethal infections of P. aeruginosa and A. baumannii and enhanced the activity of colistin in vivo against colistin-resistant P. aeruginosa.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 6953 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-017-07440-0en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-017-07440-0 (PII)en
dc.identifier.pmid28761101 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100014en
dc.identifier.volume7en
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.subjectINTRACELLULAR PATHOGENIC BACTERIAen
dc.subjectCYSTIC-FIBROSIS PATIENTSen
dc.subjectHOST-DEFENSE PEPTIDESen
dc.subjectIN-VIVOen
dc.subjectANTIBACTERIAL ACTIVITYen
dc.subjectINFECTION MODELen
dc.subjectPLAUSIBLE MODEen
dc.subjectHUMAN SERUMen
dc.subjectIDENTIFICATIONen
dc.subjectMECHANISMen
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshCaenorhabditis elegansen
dc.subject.meshBiofilmsen
dc.subject.meshAcinetobacter baumanniien
dc.subject.meshPseudomonas aeruginosaen
dc.subject.meshPseudomonas Infectionsen
dc.subject.meshCystic Fibrosisen
dc.subject.meshColistinen
dc.subject.meshAntimicrobial Cationic Peptidesen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshDrug Stabilityen
dc.subject.meshDrug Resistance, Multiple, Bacterialen
dc.subject.meshDrug Designen
dc.titleA short D-enantiomeric antimicrobial peptide with potent immunomodulatory and antibiofilm activity against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumanniien
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2017-06-28en
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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