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Ross, R. Paul Hill, Colin Field, Des O'Connor, Michelle Science Foundation Ireland 2025-01-31T14:58:39Z 2025-01-31T14:58:39Z 2024 2024 This thesis investigates antimicrobial resistance (AMR) and the potential for bacteriocins as an alternative or adjunct to traditional antibiotics. More specifically, this thesis explores the class Ia bacteriocins termed lantibiotics, and the identification and characterisation of novel bacteriocins from canine sources. Chapter 1 focuses on the current knowledge regarding the self-protection mechanisms employed by lantibiotic-producing bacteria via their lantibiotic immunity proteins. The research conducted to date on lantibiotic immunity proteins associated with production, as well as the development of lantibiotic resistance in pathogenic species is described, primarily focusing on ABC transporters. This review also discusses potential approaches to overcome lantibiotic resistance. Chapter 2 investigates the heterologous expression of the nisin immunity proteins NisI and NisFEG, and the nisin resistance proteins Nsr and NsrFP, in three Lactococcus lactis strains. One strain is nisin sensitive (MG1614), one is immune (NZ9800), and the third is both nisin producing and immune (NZ9700). This study analysed the sensitivity of these strains harbouring these immunity/resistance proteins using minimum inhibitory concentrations (MIC) assays. This study also determined whether it is possible to increase immunity or resistance to nisin by introducing extra copies of these immunity/resistance genes into strains already exhibiting nisin immunity (NZ9800) or resistance (MG1614 pNP40). The final observation in this study was on the effect of increasing nisin immunity proteins on nisin production in NZ9700. Chapter 3 investigated bioengineered nisin variants at amino acid residues 9 and 10 within ring-B of the nisin peptide. From this bank of bioengineered derivates a variant, termed nisin M, was found to retain full induction capacity, even at concentrations as high as 300 ng mL-1, while exhibiting a 4-16-fold decrease in antimicrobial activity against nisin sensitive strains. As the overall aim of this thesis was to investigate the potential for bacteriocins as alternatives or adjuncts to antibiotics, chapter 4 involved screening five canines for novel bacteriocins. A combination of in silico and in vitro analysis of eight bacterial isolates identified 14 novel bacteriocins, one of which was further characterised. This novel bacteriocin, termed caledonicin, is the first bacteriocin identified from the species Staphylococcus caledonicus and exhibits antimicrobial activity against a range of pathogens; including Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP), and the IBD/IBS associated bacteria Mediterraneibacter gnavus ATCC 29149. The final chapter of this thesis focuses on another bacteriocin identified within the screen described in chapter 4. The lanthipeptide, termed paenidicin L, is a heat stable, protease sensitive peptide which has antimicrobial activity against several indicators. Based on mass spectrometry, it is assumed the peptide consists of five or six (methyl)lanthionine rings. Overall, this thesis expands the current knowledge on induction and immunity of the most widely studied bacteriocin, nisin, as well as identifies novel bacteriocins from canine sources as potential alternatives to antibiotics in AMR. Not peer reviewed Accepted Version application/pdf O'Connor, M. 2024. Characterisation of novel bacteriocins from canine sources. PhD Thesis, University College Cork. 262 https://hdl.handle.net/10468/16950 en University College Cork 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/ info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ © 2024, Michelle O'Connor. https://creativecommons.org/licenses/by-nc-nd/4.0/ Bacteriocins Antimicrobial resistance Antimicrobial peptides Canine Resistance RiPPs Characterisation of novel bacteriocins from canine sources Doctoral thesis Doctoral PhD - Doctor of Philosophyinfo:eu-repo/semantics/openAccess