Profiling bacteriophages of the human gut and exploring their application in food and medicine

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Lewis, Rhea
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University College Cork
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Bacteriophages (phages) are viruses which infect bacteria and are ubiquitous in nature. Phage research has undergone periods of interest and indifference, but are now common tools with some suggesting that they will become important as antimicrobial agents in food and in medicine. The first chapter of this thesis is in two parts. Chapter 1a reviews the discovery, basic biology, and applications of phages. They have varied uses such as in models for predator and prey dynamics studies, as a last resort in the fight against antibiotic resistant infections, in the treatment of illness and disease by faecal transplant, in food safety, in phage display and the expression of antibodies and peptides, and in metagenomics studies to understand human health and disease. In the chapters that follow four of these applications were investigated. Chapter 1b addresses the barriers that should be taken into account in order to use phages successfully in food and feed. These issues can also arise when using phages in phage therapy. Chapter 2 investigated a commercially available phage against Listeria monocytogenes, the causative agent of a serious foodborne illness. Phages can be used as clean label additives which are becoming more accepted than traditional additives by consumers. Phage alone and in combination with a commercially available bacteriocin, a ribosomally produced antimicrobial peptide, caused a significant reduction of L. monocytogenes in a food model. In Chapter 3 the effect of hormonal contraception on the human faecal virome was investigated in a pilot study. No differences in viral or bacterial diversity were found between men and women but viral diversity was found to be reduced in women using hormonal contraception compared to women not using hormonal contraception. Clustering increased the discriminatory power of the virome data. This could be important for establishing inclusion or exclusion criteria for subjects or choosing healthy controls for studies. Chapter 4 addresses the isolation of phages and the analysis of single nucleotide polymorphisms (SNPs) in phage strains. Notwithstanding the importance of culture-independent methods for studying phages the isolation of phages is still necessary. No phages were isolated from the same source as bacterial strains but a number were isolated from environmental samples, illustrating the value of looking in different sources and new environments. 70 strains of Escherichia coli phage APCEc01 were isolated and compared to each other and the original sequenced genome of APCEc01. This highlighted the variation that occurs in genomes of the same phage and its possible impact. In Chapter 5 a jumbo phage was isolated against Klebsiella aerogenes, a member of the ESKAPE pathogens which are of concern due to their ability to cause hospital acquired and antibiotic resistant infections. The phage isolated was effective against K. aerogenes biofilms which are routinely found on medical devices. The phage in combination with Phage K was effective against a mixed biofilm of K. aerogenes and Staphylococcus aureus. Phages have myriad applications in food and medicine. Since their discovery the number and breadth of applications have continued to grow. This research highlighted these uses and investigated a number of them in greater detail. This included the use of phage as useful tools in food safety, the first study highlighting the effect of hormonal contraception on the human gut virome, the isolation of a novel phage against a clinically relevant pathogen and its application as a tool to combat biofilms, and an investigation into the isolation of phages and the incidence of single nucleotide polymorphisms in strains of phages.
Human gut phageome , Human microbiome , Virome , Phage therapy , Bacteriophage
Lewis, R. 2020. Profiling bacteriophages of the human gut and exploring their application in food and medicine. PhD Thesis, University College Cork.