Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa

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dc.contributor.authorKim, Hyunko
dc.contributor.authorJang, Ju Hyeko
dc.contributor.authorKim, Sun Changko
dc.contributor.authorCho, Ju Hyunko
dc.date.accessioned2020-01-14T07:20:12Z-
dc.date.available2020-01-14T07:20:12Z-
dc.date.created2020-01-14-
dc.date.issued2020-01-
dc.identifier.citationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.185-
dc.identifier.issn0223-5234-
dc.identifier.urihttp://hdl.handle.net/10203/271179-
dc.description.abstractThe emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa, coupled with shrinking antibiotic pipelines, has increased the demand for new antimicrobials with novel mechanisms of action. As the indiscriminate nature of broad-spectrum antimicrobial toxicity may have negative clinical consequences and increase the incidence of resistance, we have developed a P. aeruginosa-selective antimicrobial peptide capable of preferentially killing P. aeruginosa relative to benign microorganisms. A targeting peptide (PA2) that binds specifically to OprF porin on P. aeruginosa was identified by phage display peptide library screening, and a hybrid peptide was constructed by addition of the targeting peptide to GNU7, a potent antimicrobial peptide. The resulting hybrid peptide PA2-GNU7 exhibited potent antimicrobial activity against P. aeruginosa without causing host toxicity. Confocal laser scanning microscopy analysis and time-kill experiments demonstrated that PA2-GNU7 exhibited a high degree of specificity for P. aeruginosa, and rapidly and selectively killed P. aeruginosa cells in mixed cultures. In addition, in vivo treatment efficacy of PA2-GNU7 was significantly greater than that of conventional antibiotics in a mouse model of MDR P. aeruginosa infection. Taken together, the data suggest that PA2-GNU7 may be a promising template for further development as a novel anti-MDR P. aeruginosa therapeutic agent. (C) 2019 Elsevier Masson SAS. All rights reserved.-
dc.languageEnglish-
dc.publisherELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER-
dc.titleDevelopment of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa-
dc.typeArticle-
dc.identifier.wosid000503099900028-
dc.identifier.scopusid2-s2.0-85074162623-
dc.type.rimsART-
dc.citation.volume185-
dc.citation.publicationnameEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY-
dc.identifier.doi10.1016/j.ejmech.2019.111814-
dc.contributor.localauthorKim, Sun Chang-
dc.contributor.nonIdAuthorKim, Hyun-
dc.contributor.nonIdAuthorJang, Ju Hye-
dc.contributor.nonIdAuthorCho, Ju Hyun-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorAntimicrobial peptide-
dc.subject.keywordAuthorHybrid peptide-
dc.subject.keywordAuthorMultidrug-resistant Pseudomonas aeruginosa-
dc.subject.keywordAuthorOprF-
dc.subject.keywordAuthorSelective antimicrobial activity-
dc.subject.keywordPlusMEMBRANE PROTEIN OPRF-
dc.subject.keywordPlusHOST-DEFENSE PEPTIDES-
dc.subject.keywordPlusANTIBIOTICS-
dc.subject.keywordPlusPATHOGENESIS-
dc.subject.keywordPlusENHANCEMENT-
dc.subject.keywordPlusSELECTIVITY-
dc.subject.keywordPlusINFECTIONS-
dc.subject.keywordPlusRESISTANCE-
dc.subject.keywordPlusBACTERIA-
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