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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

New Phages, New Insights: Diversity in Phage Research Leads To Impactful Phage Therapy Outcomes

Harry Jack Ashbaugh (18858763) 22 June 2024 (has links)
<p dir="ltr">Bacteriophages are viruses that infect, replicate in, and kill bacteria. In industries that utilize microbes for production, like <i>E.coli</i> in the production of insulin or <i>A. globiformis</i> in the production of cheese, bacteriophages can pose a huge threat to manufacturing. However, bacteriophages aren’t entirely detrimental: we can use the destructive nature of bacteriophages to kill bacterial infections in the human body. This process is known as phage therapy, and while it isn’t a new concept, it is being seen as an increasingly necessary alternative to traditional antibiotics due to the increasing rise of antimicrobial resistance. Because bacteriophages have an entirely different mechanism of destroying bacteria, they can be used in tandem with traditional antibiotic regimens to help wipe out infections. Also, phages have a highly specific host range, meaning that an injection of a certain type of phage will only infect the bacteria it is targeting, sparing important gut microbes.</p><p dir="ltr">The search for new phages to treat infections has resulted in the discovery of over 25,000 actinobacteriophages, with about 4898 of them being sequenced. This is extremely important and necessary, but 49% of these sequenced phages are all mycobacteriophages. This bias towards mycobacteriophages is likely because they infect the genus mycobacterium, where the deadly <i>M. tuberculosis</i> resides. The discovery of new phages using less studied hosts results in novel phages that exhibit rarely seen morphologies, phenotypes, and genotypes. This leads to a better overall understanding of the phage proteome and can lead to new breakthroughs in phage therapy.</p><p dir="ltr">The purpose of this research is to study the differences between different types of phages and try to determine the impact it may have on phage therapy. This thesis is divided into three chapters. In the first chapter, novel phages from different hosts, including <i>M. smegmatis</i> and <i>A. globiformis</i>, were discovered and annotated, and the differences between them were characterized. The discovery of arthrobacteriophages immediately resulted in rare and previously unseen phage characteristics. In the second chapter, proteomic mass spectrometry data of various diverse mycobacteriophages was analyzed to determine differences. Despite being from multiple clusters and lifecycles, the expression data had more similarities than differences. In the third chapter, an alternative method of extracting DNA from phages is explored to determine the result of discrepancies in gel quality from <i>M. smegmatis</i> and <i>A. globiformis.</i><i> </i>Although a large amount of nucleic material was derived, it was not stable DNA and was unsuitable for use. The reason for poor gel quality is still unknown.</p>

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