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Bioengineering of nisin to enhance functionality against dairy pathogens
Healy, Brian
The bacteriocin class of antimicrobial peptides have emerged as a viable alternative to at least partially fill the void created by the end of the golden age of antibiotic discovery. Along with this potential use in a clinical setting, bacteriocins also play an important role as bio-preservatives in the food industry. This thesis focuses on a specific bacteriocin group, the lantibiotics (Lanthionine-containing antibiotics). Their numerous methods of appliance in a food setting and how their gene-encoded nature can be modified to improve on overall bioactivity and functionality are explored here. The use of a lantibiotic (lacticin 3147) producing starter culture to control the Crohn’s disease-linked pathogen Mycobacterium paratuberculosis was assessed in a raw milk cheese. Although lacticin 3147 production did not effectively control the pathogen, the study provided an impetus to employ a variety of PCR-based mutagenesis techniques with a view to the creation of enhanced lantibiotic derivatives. Through the use of these techniques, a number of enhanced derivatives were generated from the ‘hinge’ region of the nisin peptide. Furthermore, a derivative in which the three hinge amino acids were replaced with three alanines represents the first enhanced derivative of nisin to have been designed through a rational process. This derivative also formed the backbone for the creation of an active, trypsin resistant, variant. Through the employment of further mutagenesis methods a derivative was created with potential use as an oral anti-bacterial in the future. Finally a number of lead nisin derivatives were investigated to assess their anti- Streptococcus agalactiae ability, a mastitis associated pathogen. Also a system was developed to facilitate the large scale production of these candidates, or other nisin derivatives, from dairy substrates.
Keyword(s): Nisin; Lacticin 3147; Bacteriocin; Lantibiotic; Mutagenesis; Bioengineering; Streptococcus agalactiae; Mycobacterium avium subspecies paratuberculosis; Lactococcus lactis
Publication Date:
2014
Type: Doctoral thesis
Peer-Reviewed: No
Language(s): English
Institution: University College Cork
Funder(s): Teagasc
Citation(s): Healy, B. C. 2014. Bioengineering of nisin to enhance functionality against dairy pathogens. PhD Thesis, University College Cork.
Publisher(s): University College Cork
File Format(s): application/pdf
Supervisor(s): Hill, Colin
Cotter, Paul D.
Ross, R. Paul
First Indexed: 2016-07-13 05:49:35 Last Updated: 2017-09-06 06:30:35