Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Applied Mathematics

Supervisor

Lindi Wahl

Abstract

In this investigation, we examined the interaction of phages and bacteria in bacterial biofilm colonies, the evolution of prophages (viral genetic material inserted into the bacterial genome) and their genetic repertoire. To study the synergistic effects of lytic phages and antibiotics on bacterial biofilm colonies, we have developed a mathematical model of ordinary differential equations (ODEs). We have also presented a mathematical model consisting of a partial differential equation (PDEs), to study evolutionary forces acting on prophages. We fitted the PDE model to three publicly available databases and were able to show that induction is the prominent fate of intact prophages, with an average prophage loss of only 1% of its genome before induction. We also demonstrate that there is a tipping point at which the relation between prophage and bacteria transforms from being parasitic to mutualistic. Lastly, we investigated annotated prophages from two well-studied prophage databases. These genes were accessed using PHASTER, a bioinformatics tool to identify prophages in bacterial genomes. From this analysis, we observed that genes involved in phage lytic function are preferentially lost, while integrase and transposase are preferentially enriched in smaller prophages. We have also developed an ODE model and have carried out gene-level simulations to get more insight into the genetic repertoire of prophages. The results of our ODE model and gene-level simulations are in agreement with prophage repertoire data.

Summary for Lay Audience

Bacteriophages are viral predators of bacteria. Upon infecting bacteria, bacteriophages either kill the host bacteria or enter a long-term genetic association with the bacterial host. The ability of bacteriophages to kill bacterial cells is used as a therapeutic strategy to cure bacterial infections, called phage therapy. If the bacteriophage enters a long-term association with the host, the viral genome integrated into the host bacterial genome is called a prophage. In this investigation, using mathematical modeling approaches, we study the synergistic effects of phage therapy and antibiotics on bacterial biofilm colonies, the evolution of prophages and the genetic composition of prophages.

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