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The effect of a beta-lactamase inhibitor peptide on bacterial membrane structure and integrity: a comparative study

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dc.contributor.authorSARIYAR AKBULUT, BERNA
dc.contributor.authorsAlaybeyoglu, Begum; Uluocak, Bilge Gedik; Akbulut, Berna Sariyar; Ozkirimli, Elif
dc.date.accessioned2022-03-12T20:32:54Z
dc.date.available2022-03-12T20:32:54Z
dc.date.issued2017
dc.description.abstractCo-administration of beta-lactam antibiotics and beta-lactamase inhibitors has been a favored treatment strategy against beta-lactamase-mediated bacterial antibiotic resistance, but the emergence of beta-lactamases resistant to current inhibitors necessitates the discovery of novel non-beta-lactam inhibitors. Peptides derived from the Ala46-Tyr51 region of the beta-lactamase inhibitor protein are considered as potent inhibitors of beta-lactamase; unfortunately, peptide delivery into the cell limits their potential. The properties of cell-penetrating peptides could guide the design of beta-lactamase inhibitory peptides. Here, our goal is to modify the peptide with the sequence RRGHYY that possesses beta-lactamase inhibitory activity under in vitro conditions. Inspired by the work on the cell-penetrating peptide pVEC, our approach involved the addition of the N-terminal hydrophobic residues, LLIIL, from pVEC to the inhibitor peptide to build a chimera. These residues have been reported to be critical in the uptake of pVEC. We tested the potential of RRGHYY and its chimeric derivative as a beta-lactamase inhibitory peptide on Escherichia coli cells and compared the results with the action of the antimicrobial peptide melittin, the beta-lactam antibiotic ampicillin, and the beta-lactamase inhibitor potassium clavulanate to get mechanistic details on their action. Our results show that the addition of LLIIL to the N-terminus of the beta-lactamase inhibitory peptide RRGHYY increases its membrane permeabilizing potential. Interestingly, the addition of this short stretch of hydrophobic residues also modified the inhibitory peptide such that it acquired antimicrobial property. We propose that addition of the hydrophobic LLIIL residues to the peptide N-terminus offers a promising strategy to design novel antimicrobial peptides in the battle against antibiotic resistance. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
dc.identifier.doi10.1002/psc.2986
dc.identifier.eissn1099-1387
dc.identifier.issn1075-2617
dc.identifier.pubmed28299853
dc.identifier.urihttps://hdl.handle.net/11424/234444
dc.identifier.wosWOS:000399700500002
dc.language.isoeng
dc.publisherWILEY
dc.relation.ispartofJOURNAL OF PEPTIDE SCIENCE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectbeta-lactamase
dc.subjectantibiotic resistance
dc.subjectdelivery
dc.subjectantimicrobial peptide
dc.subjectcell-penetrating peptide
dc.subjectCELL-PENETRATING PEPTIDES
dc.subjectAMOXICILLIN-CLAVULANIC ACID
dc.subjectVIVO PROTEIN TRANSDUCTION
dc.subjectANTIMICROBIAL PEPTIDES
dc.subjectESCHERICHIA-COLI
dc.subjectIN-VIVO
dc.subjectSTREPTOCOCCUS-PNEUMONIAE
dc.subjectANTIBACTERIAL ACTIVITY
dc.subjectSTAPHYLOCOCCUS-AUREUS
dc.subjectDRUG DISCOVERY
dc.titleThe effect of a beta-lactamase inhibitor peptide on bacterial membrane structure and integrity: a comparative study
dc.typearticle
dspace.entity.typePublication
local.avesis.id80520ba1-a665-4081-8796-184f70662a5e
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages10
local.journal.quartileQ3
oaire.citation.endPage383
oaire.citation.issue5
oaire.citation.startPage374
oaire.citation.titleJOURNAL OF PEPTIDE SCIENCE
oaire.citation.volume23
relation.isAuthorOfPublicationa9f127d3-8332-44dd-a532-34f3ef20bdb5
relation.isAuthorOfPublication.latestForDiscoverya9f127d3-8332-44dd-a532-34f3ef20bdb5

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