Growth dynamics of E. coli in the presence of cell wall-targeting antibiotics

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.