Growth dynamics of E. coli in the presence of cell wall-targeting antibiotics
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Date
26/11/2019Author
Brouwers, Rebecca
Metadata
Abstract
This thesis investigates the growth dynamics of Escherichia coli bacteria in the
presence of cell wall-targeting antibiotics, using experiments and mathematical
modelling in order to understand quantitatively how these antibiotics interact
with growing bacterial cells. In the experiments E. coli were grown in various
growth media (which result in different growth rates), with a range of antibiotic
concentrations. Measurements of optical density and viable colony counts
revealed complex growth medium-dependent inhibition dynamics for the different
antibiotics, contrary to the “standard” picture that cell wall-targeting antibiotics
are more effective against fast growing bacteria. Complementary microscopy
analysis suggested a strong correlation between the antibiotic mechanism of action
and changes in cell morphology, and consequently the population’s inhibition
dynamics.
To link the mechanism of antibiotic action to bacterial population dynamics, a
mathematical model is presented, guided by the experiments. The model is able
to reproduce the inhibition dynamics and morphological changes observed in the
presence of mecillinam and aztreonam. The model’s robustness and generality
is tested by applying it to other growth conditions, to other antibiotics such
as fosfomycin, and to combinations of antibiotics. The model performs very
well, capturing many of the inhibition dynamics and morphology changes as
observed experimentally, as well as testing different hypotheses for the mechanism
triggering division in E. coli.
In summary this thesis presents a unified experimental and theoretical approach
to understanding the effects of cell wall-targeting antibiotics on growing bacterial
cells.