This dissertation investigates the diversity and competition of nucleus-forming jumbo phage. The first chapter provides a brief history of the discovery of bacteriophages and their early use to combat bacterial infections, the detection of the first jumbo phages, the first characterizations of nucleus-forming jumbo phage, current understanding of viral speciation, a background of phage-encoded mobile introns, the theory of Viral Eukaryogenesis, and the recent resurgence of phage therapy. Chapter 2 describes the conservation and divergence of the nucleus-forming jumbo phage replication cycle in E. coli phage Goslar. Fluorescent microscopy supported with cryo-electron tomography of focused ion beam-milled samples (cryo-FIB-ET) revealed the organization and kinetics of Goslar infection. Genetics were used to deduce the function of the cytoskeleton found to assemble into a vortex-like array. Chapter 3 analyzes the intracellular interactions between coinfecting phages ΦKZ and ΦPA3 in Pseudomonas aeruginosa. Two viral speciation factors were newly defined as Subcellular Genetic Isolation and Virogenesis Incompatibility which can be universally applied to viruses. Fluorescent microscopy illuminated the intracellular competition and long-term fitness against the host was assayed to demonstrate the effects of incompatibility. Chapter 4 builds on Chapter 3 to investigate the mechanism of action of one of the virogenesis incompatibility factors that is produced by ΦPA3 and interferes with ΦKZ infection. Bioinformatic analyses combined with genetics and in vitro evidence uncovered the nature and mechanism of the ΦPA3 factor. The consequences for ΦKZ were clarified by cryo-FIB-ET. Chapter 5 is a conclusion of the findings presented in this dissertation and a discussion of the way that nucleus-forming jumbo phage can address the antibiotic resistance crisis as well as the big question of how our earliest eukaryotic ancestor came into existence.
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