{"doi":"10.1111/mmi.14183","title":"Bioengineering nisin to overcome the nisin resistance protein","abstract":"<jats:title>Summary</jats:title><jats:p>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 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.</jats:p>","journal":"Molecular Microbiology","year":2019,"id":666625,"datarank":0.6329261557764161,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":0.0,"self_endowment_contribution":0.6329261557764161,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1200812,"name":"Tony Blake","orcid":null,"position":1,"is_corresponding":false},{"id":1740890,"name":"Harsh Mathur","orcid":null,"position":2,"is_corresponding":false},{"id":1740891,"name":"Paula M. 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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 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.</jats:p>","is_dataset_classified":null,"base_score":4.219507705176107,"endowment":4.219507705176107,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30537404","pmcid":null,"openalex_id":"https://openalex.org/W2904410259","authors":[],"funders":[{"funder_name":"Science Foundation Ireland","grant_id":"10/IN.1/B3027","title":"Lantibiotics: the next generation"},{"funder_name":"Science Foundation Ireland","grant_id":"11/PI/1137","title":"Obesibiotics"},{"funder_name":"Science Foundation Ireland","grant_id":"14/TIDA/2286","title":"Nis-2-Gen: Developing Second Generation Nisin’s with Therapeutic Applications."},{"funder_name":"Science Foundation Ireland","grant_id":"SFI/12/RC/2273","title":null}],"total_grants":4,"fwci":7.1476,"citation_percentile":0.97202334,"influential_citations":0,"citation_trend":[{"year":2019,"count":7},{"year":2020,"count":12},{"year":2021,"count":12},{"year":2022,"count":7},{"year":2023,"count":12},{"year":2024,"count":7},{"year":2025,"count":5},{"year":2026,"count":5}],"oa_status":"bronze","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.14183","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.14183","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/mmi.14183","host_type":"publisher"},{"url":"https://doi.org/10.1111/mmi.14183","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30537404","host_type":"repository"},{"url":"http://hdl.handle.net/10468/7231","host_type":"repository"},{"url":"http://hdl.handle.net/11019/2999","host_type":"repository"},{"url":"https://dx.doi.org/10.1111/mmi.14183","host_type":""},{"url":"https://hdl.handle.net/10468/7231","host_type":""}],"fields_of_study":["Probiotics and Fermented Foods","Bacteriophages and microbial interactions","Transgenic Plants and Applications","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Anti-Bacterial Agents","Bacterial Proteins","Food Preservatives","Lipoproteins","Membrane Proteins","Microbial Sensitivity Tests","Nisin","Drug Resistance, Bacterial","Bioengineering"],"keywords":["Nisin","Biology","Microbiology","Antimicrobial","nisin A S29P","Nisin PV","Bacteriocin","Lipoproteins","Membrane Proteins","Bioengineering","Microbial Sensitivity Tests","nisin resistance protein","Bacterial resistance","Lantibiotic","Anti-Bacterial Agents","Bacterial Proteins","Antibiotic resistant bacteria","Drug Resistance, Bacterial","Food Preservatives","Antimicrobial peptide"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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