Bioengineering nisin to overcome the nisin resistance protein

Thumbnail Image
8592.pdf(693.74 KB)
Accepted version
8592_1.pdf(1.73 MB)
Supporting information
Field, Des
Blake, Tony
Mathur, Harsh
O'Connor, Paula M.
Cotter, Paul D.
Ross, R. Paul
Hill, Colin
Journal Title
Journal ISSN
Volume Title
Published Version
Research Projects
Organizational Units
Journal Issue
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.
Bacterial resistance , Nisin resistance protein , Antimicrobial peptide , Nisin , Lantibiotic , Bacteriocin
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
© 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 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.