Bioengineering nisin to overcome the nisin resistance protein

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dc.contributor.author Field, Des
dc.contributor.author Blake, Tony
dc.contributor.author Mathur, Harsh
dc.contributor.author O'Connor, Paula M.
dc.contributor.author Cotter, Paul D.
dc.contributor.author Ross, R. Paul
dc.contributor.author Hill, Colin
dc.date.accessioned 2018-12-17T15:03:28Z
dc.date.available 2018-12-17T15:03:28Z
dc.date.issued 2018-12-11
dc.identifier.citation Field, D., Blake, T., Mathur, H., O'Connor, P. M., Cotter, P. D., Ross, R. P. and Hill, C. (2018) 'Bioengineering Nisin to overcome the Nisin Resistance Protein', Molecular Microbiology, In Press, doi: 10.1111/mmi.14183 en
dc.identifier.startpage 1 en
dc.identifier.endpage 36 en
dc.identifier.issn 0950-382X
dc.identifier.issn 1365-2958
dc.identifier.uri http://hdl.handle.net/10468/7231
dc.identifier.doi 10.1111/mmi.14183
dc.description.abstract The emergence and dissemination of antibiotic resistant bacteria is a major medical challenge. Lantibiotics are highly modified bacterially produced antimicrobial peptides that have attracted considerable interest as alternatives or adjuncts to existing antibiotics. Nisin, the most widely studied and commercially exploited lantibiotic, exhibits high efficacy against many pathogens. However, some clinically relevant bacteria express highly specific membrane‐associated nisin resistance proteins. One notable example is the nisin resistance protein (NSR) that acts by cleaving the peptide bond between ring E and the adjacent serine 29, resulting in a truncated peptide with significantly less activity. We utilised a complete bank of bioengineered nisin (nisin A) producers in which the serine 29 residue has been replaced with every alternative amino acid. The nisin A S29P derivative was found to be as active as nisin A against a variety of bacterial targets but, crucially, exhibited a 20‐fold increase in specific activity against a strain expressing the nisin resistance protein. Another derivative, nisin PV, exhibited similar properties but was much less prone to oxidation. This version of nisin with enhanced resistance to specific resistance mechanisms could prove useful in the fight against antibiotic resistant pathogens. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Wiley en
dc.relation.uri https://onlinelibrary.wiley.com/doi/abs/10.1111/mmi.14183
dc.rights © 2018 This article is protected by copyright. All rights reserved. This is the peer reviewed version of the following article: (2018), ‘Bioengineering Nisin to overcome the Nisin Resistance Protein’, Mol Microbiol. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1111/mmi.14183. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. en
dc.subject Bacterial resistance en
dc.subject Nisin resistance protein en
dc.subject Antimicrobial peptide en
dc.subject Nisin en
dc.subject Lantibiotic en
dc.subject Bacteriocin en
dc.title Bioengineering nisin to overcome the nisin resistance protein en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Colin Hill, Microbiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: c.hill@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2019-12-11
dc.date.updated 2018-12-17T14:51:37Z
dc.description.version Accepted Version en
dc.internal.rssid 465912052
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Microbiology en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress c.hill@ucc.ie en
dc.internal.bibliocheck In Press Dec 2018. Update citation and copyright details. Add vol, update page nos. en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/14/TIDA/2286/IE/Nis-2-Gen: Developing Second Generation Nisin_s with Therapeutic Applications./ en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA) - Training Award/10/IN.1/B3027 TIDA Training 11/IE/Lantibiotics: the next generation/ en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/11/PI/1137/IE/Obesibiotics/ en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en


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