This Is AuburnElectronic Theses and Dissertations

The Phage Behind the Curtain: Determining the Role of Bacteriophage in the Restructuring of Microbiomes During Disease

Date

2021-11-30

Author

Hallowell, Haley

Type of Degree

PhD Dissertation

Department

Biological Sciences

Restriction Status

EMBARGOED

Restriction Type

Auburn University Users

Date Available

11-30-2022

Abstract

The gut microbiome is a dynamic microbial ecosystem inhabited by all domains of life and is essential for the homeostatic function of almost all organ systems within the host. Additionally, the mammalian intestine is home to the largest immune network within the body and is tasked with the challenge of maintaining tolerance to commensal microorganisms while also retaining the ability to respond to invading pathogens. In steady state, the gut microbiome is dominated with Bacteria and Bacteriophage, with smaller populations of Archaea and Eukaryotes. In times of disease, such as Obesity, there is a deviation from the steady-state composition of the microbiome that potentially worsens the severity of disease. Though many studies have explored the link between the microbiome and disease state, many questions remain unanswered. For example, much less is known about how other constituents, such as Bacteriophage, contribute to disease. Further, many of these studies focused on the connection between the microbiome and the fully developed disease. Therefore, the purpose of this dissertation was to determine how bacteriophage might change and contribute to the development of disease and disentangle a possible mechanism by which this occurs. Using a novel model of obesity, the Mangalica pig, I found that bacteriophage populations rapidly change in response to the development of obesity, while bacterial populations were much more resilient over the course of 18 weeks. Obesity is associated with low-grade, chronic inflammation. Therefore, I also aimed to determine how immune products might lead to changes in bacteriophage populations seen during obesity. To do this, I characterized bacteriophage reproduction in the presence or absence of immune stressors in two different bacteriophage species: the virulent bacteriophage PF2 and the temperate bacteriophage Lambda. I found that immune stressors inhibited adsorption of PF2, but not Lambda, to its host in a dose-dependent manner. Additionally, hydrogen peroxide, but not hypochlorous acid, decreased progeny production in PF2. Finally, hydrogen peroxide, but not hypochlorous acid, led to an increase in prophage activation in bacteriophage Lambda. Taken together, my dissertation highlights the intricacy and interplay between bacteria and bacteriophage during the development of disease.