Master's thesis defense by Rasmus Skytte Eriksen – Niels Bohr Institute - University of Copenhagen

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Master's thesis defense by Rasmus Skytte Eriksen

Quantitative modelling of spacio-temporal structure in phage-bacteria interaction

Abstract:
This thesis investigates how the structure of a bacterial microcolony could offer physical
shielding against a phage (:virus) attack. From agent-based simulations of individual
phage and cells, I show that the phage invasion is limited by a constant penetration
depth into the microcolony. As a consequence, the bacterial microcolony can continue to grow while being attacked if it is initially above a critical size. The influence of the phage parameters on this critical size is investigated, and I find that parameters which increase the production rate of the phage increases the critical size. This includes increasing the number of new phage produced per cell lysis (:cell death), or decreasing the time it takes for a phage to lyse a cell. Likewise, I find that the critical size increases, when the penetration ability of the individual phage increases, as is the case when the adsorption rate decreases.
Temperate phage sometimes form lysogens when infecting a susceptible host, and these lysogens prevent subsequent phage infections from proliferating. Using the simulations I show that when the phage are temperate, the lysogens acts as sinks for the phage which increases the effectiveness of the physical shielding. These lysogen drastically reduce the density of free phage outside the microcolony and thereby protects the neighboring microcolonies.
I developed a phenomenological model to describe colony growth under the phage
attack. I have found the model to match nicely with the numerical simulations.
The existence of a critical size is supported with experimental evidence. By growing
Escherichia coli for varying times before introducing the virulent phage P1vir to the
colonies, we show that E. coli colonies cannot survive a phage attack if they have grown
less than 6 h before the phage arrived at the colony, whereas all colonies which had
grown 6 h or more when the phage arrived grows to be much larger and has surviving
cells in the colony.