Characterisation of bacteriophage dynamics associated with foodborne pathogens

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dc.check.chapterOfThesisChapter 5. In vivo Coexistence of Phages and Citrobacter rodentium During Gut Colonisationen
dc.check.date2031-05-31
dc.check.infoControlled Access, Partial Restriction
dc.contributor.advisorHill, Colin
dc.contributor.advisorRoss, R. Paul
dc.contributor.authorShareefdeen, Hibaen
dc.contributor.funderHORIZON EUROPE Marie Sklodowska-Curie Actionsen
dc.date.accessioned2026-01-29T14:37:04Z
dc.date.available2026-01-29T14:37:04Z
dc.date.issued2025
dc.date.submitted2025
dc.descriptionControlled Access, Partial Restriction
dc.description.abstractBacteriophages (phages) are viruses that infect bacteria and are found in high abundance in the gut. As antimicrobial resistance rises and interest in microbiome-targeted therapies grows, phages have emerged as potential tools for precisely modulating microbial communities and treating infections. However, much remains unknown about how phages behave in the gut ecosystem where microbial dynamics are complex and are influenced by host factors and acute events such as foodborne infections. This thesis explores the ecological roles and therapeutic potential of phages in the gut, with a particular focus on phage-bacteria interactions involving foodborne pathogens. Using models that incorporate phage interactions with both pathogens and commensal bacteria this thesis explores the way in which phages can impact bacterial colonisation and colonisation resistance. To establish the conceptual and translational context of this work, the emerging role of the gut virome in health and disease is reviewed, highlighting the virome as both a potential biomarker of disease and a component of microbiome shifts. Novel associations have been identified between the human gut virome and diseases such as obesity, necrotizing enterocolitis and SARS-CoV-2 infection. Next, recent advances in phage therapy are reviewed, including synthetic biology approaches, personalized phage cocktails, and delivery innovations that aim to overcome the limitations of traditional phage use. The experimental component of this thesis focuses on the isolation and characterisation of phages infecting foodborne pathogens as well as in vivo and in vitro experiments investigating the role that phages play in bacterial colonisation. The isolation and characterisation of novel phages infecting Escherichia coli and Listeria monocytogenes is described. Phages were obtained from environmental samples and tested for lytic activity, host range, and stability to assess their potential as candidates for future studies in phage therapy, biocontrol, and food safety applications. Genome sequencing of the phages revealed additional insights including the identification of a novel jumbo E. coli phage and the establishment of a new Listeria phage genus, Aquingentivirus. A Citrobacter rodentium mouse infection model was used to study the impact of phage treatment in vivo. C. rodentium is a widely used model for human enteropathogenic and enterohaemorrhagic E. coli. Interestingly, phage administration in vivo did not eliminate C. rodentium but instead led to a stable phage-bacteria coexistence. Phage replication in the gut occurred at high levels without reducing bacterial load or infection-associated inflammation. This underscores the influence that spatial structure, host factors, and bacterial heterogeneity may have on phage efficacy in the gut environment. Finally, the mechanism by which phages may alter colonisation resistance and microbiome composition was investigated. Introducing phages targeting an individual member within a defined community revealed that phage-mediated modulation of one member could have cascading effects on pathogen susceptibility. In particular, targeting Enterococcus faecalis with phages allowed L. monocytogenes to persist, illustrating how phages can indirectly shape colonisation outcomes. Similar to the findings from the C. rodentium animal experiments, phage-bacteria co-existence occurred at high-titres in vitro in the simplified model community. Taken together, the work presented here highlights that while some phages are effective at killing bacteria in vitro, their in vivo dynamics are shaped by factors such as ecological context and host-microbiota interactions. These findings have implications for the design of phage-based therapies and for understanding how the gut virome can influence susceptibility to foodborne infection. This work provides insights into gut phage ecology and contributes to a growing framework for using phages as tools for microbiome manipulation and infection control.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationShareefdeen, H. 2025. Characterisation of bacteriophage dynamics associated with foodborne pathogens. PhD Thesis, University College Cork.
dc.identifier.endpage237
dc.identifier.urihttps://hdl.handle.net/10468/18491
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/956279/EU/Colonization resistance: training and research towards microbiome derived solutions to foodborne disease/COL_RESen
dc.rights© 2025, Hiba Shareefdeen.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBacteriophage
dc.subjectMicrobiome
dc.subjectColonisation resistance
dc.subjectPhage therapy
dc.titleCharacterisation of bacteriophage dynamics associated with foodborne pathogens
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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