자료유형 | 학위논문 |
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서명/저자사항 | Evolution of Bacteriophages Infecting Enterococcus from the Human Microbiome. |
개인저자 | Wandro, Stephen Joseph. |
단체저자명 | University of California, Irvine. Biological Sciences - Ph.D.. |
발행사항 | [S.l.]: University of California, Irvine., 2019. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
형태사항 | 175 p. |
기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
ISBN | 9781085656085 |
학위논문주기 | Thesis (Ph.D.)--University of California, Irvine, 2019. |
일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Whiteson, Katrine. |
이용제한사항 | This item must not be sold to any third party vendors. |
요약 | Enterococcus can be both a friend and a foe in the human microbiome. As an opportunistic pathogen, Enterococcus is normally benign. However, Enterococcus is responsible for many hospital-acquired infections and has shown rising rates of vancomycin resistance. Bacteriophages (phages) could be an alternative to antibiotics to target these antibiotic resistant bacteria, but the evolutionary and phenotypic outcomes of phage-bacteria interactions need to be investigated more thoroughly.We begin by investigating the gut microbiome of preterm infants that had been exposed to antibiotics to learn about the scenarios in which Enterococcus blooms occur in the gut (Chapter 1). We show that antibiotic exposed gut microbiomes are dominated by facultative anaerobes such as Enterococcus and Enterobacteriaceae. Further, we show that the bacterial composition is correlated to the overall metabolite profile. Metabolomics is a powerful tool for investigating microbial metabolism, and we contribute to the effort of developing standardized practices for metabolomics in the human microbiome by showing that freezing microbial samples required for long term storage (Chapter 2).Next, we investigated how phages could be used as therapeutics for treating Enterococcus blooms and infections (Chapters 3, 4, and 5). When Enterococcus is grown with its phages in vitro, it evolves resistance to phage infection by mutating exopolysaccharide synthesis genes. These mutations alter the exopolysaccharides on the surface of the bacterial cell to prevent binding of phage. Further, this mechanism of resistance appears to be a general mechanism leading to resistance against a diverse array of phages. This work demonstrates that experimental evolution is a powerful tool for characterizing interactions between bacteria and phages.Phage therapy is often administered as a cocktail of multiple phages, but there are no rules or best practices described for combining phages to be most effective. We show that in vitro, Enterococcus phage cocktails are more effective at preventing the growth of phage-resistant mutants, but the composition of the cocktail is important. Genetically diverse phage cocktails performed better than cocktails of related phages. My work demonstrates some of the outcomes of phage-Enterococcus interactions and will move us closer to applying phage therapy to treat Enterococcus infections. |
일반주제명 | Microbiology. Virology. Evolution & development. Physiology. Immunology. Public health. Health sciences. Toxicology. |
언어 | 영어 |
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