Mathematical modelling of Pseudomonas aeruginosa: considering the antibiotic-induced morphological transition to improve treatment strategies

Spalding, Chloe (2019). Mathematical modelling of Pseudomonas aeruginosa: considering the antibiotic-induced morphological transition to improve treatment strategies. University of Birmingham. Ph.D.

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Abstract

Antimicrobial resistance is an urgent global health threat. It is critical that we understand how bacteria respond to antibiotics in order to formulate alternative treatment strategies to combat bacterial infections. beta-lactam antibiotics are known to induce a morphological transition in Pseudomonas aeruginosa populations; the bacteria shed the cell wall and make the reversible transition from the native rod shape to a fragile spherical shape, consequently evading the effects of the antibiotic.

Through the formulation and analysis of mathematical models, this thesis investigates the impact of the morphological transition during the growth of P. aeruginosa infections. Our results suggest that the immune system may play a vital role in clearing persistent spherical populations. By analysing suitable parameter spaces, we show that the interplay between the immune response and the spherical cells could determine the success of combined treatments. We investigate the use of genetic algorithms to obtain tailored treatment strategies and show the need to consider the morphological transition when applying this method to P. aeruginosa infections. We advocate the use of an antivirulence drug in combination with antibiotics or antimicrobial peptides as a sequential therapy to eliminate P. aeruginosa infections in which the morphological transition occurs.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):