Discovery and characterisation of bacteriocins from microbiomes

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dc.check.infoControlled Access
dc.contributor.advisorRoss, R. Paul
dc.contributor.advisorHill, Colin
dc.contributor.authorHourigan, Daviden
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2025-02-18T12:01:02Z
dc.date.available2025-02-18T12:01:02Z
dc.date.issued2024en
dc.date.submitted2024
dc.descriptionControlled Access
dc.description.abstractBacteria are social microorganisms that inhabit every corner of the world. They rarely live in isolation and are key members of the microbiome along with viruses, archaea, protozoa and algae. Microbiome research has exploded over the past 20 years, but we are only starting to disentangle the complexity and dynamic nature it holds. Bacteriocins are antimicrobial peptides produced by bacteria across the bacterial kingdom. They have gained attention as a suitable alternative or adjunct to traditional antibiotics due to low levels of documented resistance. However, the roles they play in shaping the microbiome or acting as selfish genetic elements are often overlooked when studying them through such a narrow scope. While it is widely accepted that these peptides can be exploited to target specific bacterial species, their abundance and diversity is often under explored. These factors will have a huge impetus on their suitability to be used as antimicrobials. In Chapter 1, we perform a literature review describing recent advancements in enterococcal genomics and how it’s advancements can aid in therapeutic strategy. Clinically problematic Enterococcus faecium are promiscuous with respect to horizontal gene transfer and are becoming a global healthcare issue. The ability to expand its own genome and rapidly mutate has made this bacterium resistant to multiple antibiotics. Therefore we explore non-antibiotic interventions, including bacteriocins, to tackle these pathogenic bacteria. However, in Chapter 2 we show that E. faecium APC1031 rapidly becomes resistant to the potent class IIa bacteriocin avicin A. We generated mutants at a frequency of approximately 1e-06 suggesting that class IIa bacteriocins alone may not be suitable to target such a “hardy” and adaptable bacterium. Over the past century bacteriocin research has been skewed towards the Bacillota. However, the Actinomycetota are gathering interest as an underexploited bacteriocin-producing phylum. In Chapter 3 we discover novel aureocin A53-like bacteriocins found within this phylum. We also show they are found in microbiomes. We then synthetise the first aureocin A53-like bacteriocins from Actinomycetota and show that they have antimicrobial activity. Chapter 4 explores the rumen microbiome as a source of novel bacteriocins by genome mining the Hungate1000 culture collection of rumen strains. We discover that between 30-70% of bacteria found in the rumen produce at least one bacteriocin which is more than double previous estimates of the bacteria found in mammalian gastrointestinal tract. Nisin is the most well studied bacteriocin. It is gathering attention as a suitable alternative to antibiotics. However, little is known of how widespread the genes responsible for its production are. In Chapter 5 we discover widespread nisin-like bacteriocin production genes and show they are on mobile genetic elements and present in bacteria of aetiological concern. We also show that some of these peptides can be heterologously expressed and that they have antimicrobial activity. We then show that nisin VP is a novel nisin variant from an anaerobic bacterium isolated from the pig gut. Chapter 6 shows that two Streptococcus devriesei strains have the genetic capability to produce a conserved novel circular bacteriocin. This novel bacteriocin streptocyclin BTW is an amylocyclicin-like bacteriocin found within the genus streptococcus. Both strains with the genetic capacity to produce this bacteriocin are found in the oral microbiota. The role of bacteriocins as antimicrobial peptides is a well-studied trait. However, little is known of the genetic systems that localise near them within genomes. In Chapter 7, we search for genes encoding protein families that have co-localised near lanthipeptide biosynthetic gene clusters and discover an enrichment of anti-phage defence systems. This suggests lanthipeptide production may be attribute to bacteriophage-bacteria interactions. This thesis explored the diversity of bacteriocin gene clusters that are found in microbiomes. We have shown that these peptides have antimicrobial activity in vitro. However, their abundance and diversity implies they play multiple roles in complex microbiomes.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHourigan, D. E. 2024. Discovery and characterisation of bacteriocins from microbiomes. PhD Thesis, University College Cork.
dc.identifier.endpage325
dc.identifier.urihttps://hdl.handle.net/10468/17061
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres Programme::Phase 2/12/RC/2273_P2/IE/APC_Phase 2/en
dc.rights© 2024, David Hourigan.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBacteriocin
dc.subjectMicrobiome
dc.subjectMicrobiology
dc.subjectAntimicrobial
dc.subjectEnterococcus
dc.titleDiscovery and characterisation of bacteriocins from microbiomesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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