In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Quantitative Biosciences

in the

School of Biological Sciences

Andreea Magalie

Will defend her dissertation
Bacterial dormancy and its impact on phage-host interactions

10th July 2023

8:00 AM EST

https://gatech.zoom.us/j/9121784063

Thesis advisor:

Joshua Weitz, PhD, School of Biological Sciences and School of Physics
Georgia Institute of Technology

Committee members:

Jay Lennon, PhD, Department of Biology, Indiana University

Sam Brown, PhD, School of Biological Sciences, Georgia Institute of Technology

Rachel Kuske, PhD, School of Mathematics, Georgia Institute of Technology

Jennifer Curtis, PhD, School of Physics, Georgia Institute of Technology

Abstract:

Bacteria often face unfavorable environmental conditions and have developed numerous strategies to increase their survival. One common survival strategy employed by bacteria is dormancy. Bacterial dormancy is a reversible, low metabolic state that can be found in several forms across different bacterial species. Dormancy plays an essential role in stabilizing populations, maintaining genetic diversity and can facilitate survival in the most harsh environmental conditions. While the ecological and evolutionary benefits of dormancy have been extensively studied, limited attention has been given to its impact on bacteria-virus interactions. Recent studies highlight a relationship between spore-forming bacteria and phages, with further work needed to understand how phages can manipulate sporulation decisions in the host.

This thesis explores how dormancy changes the infection dynamics between bacteria and viruses. To answer this question, we use both modeling and experimental frameworks. We perform plaque assays to infer the infection dynamics in a spatial setting and use Bacillus subtilis as the model organism due to its well-studied nature and the ease of distinguishing spores from actively growing cells. By using systems of ODEs and PDEs we can explore the impact of dormancy in well mixed and spatial settings. The mathematical models are designed with broad applications in mind and can be readily adapted to explore multiple types of host and phage species.

In the first part, we show that dormancy can stabilize phage-driven oscillations in well-mixed models. This result leads to an increased coexistence space between host and phages. Building upon the fundamental homogeneous models, we further investigate the effects of dormancy within spatial systems. Through plaque assays, we find that dormancy limits phage dispersion and that dormancy is enhanced in the proximity of phages. Utilizing mathematical models, we concluded that viruses induce sporulation either directly or indirectly, through the cell lysate release of a messenger molecule. In the last part, we built a mathematical model to compute optimal initiation and resuscitation probabilities given delays to initiate dormancy and environmental fluctuations. Collectively, these findings highlight the broader implications of dormancy beyond survival during adverse environmental conditions and show the significant effects dormancy can have on bacteria-virus infection dynamics.