Investigating the variability of Bordetella pertussis growth

: (Alternative Format Thesis)

Abstract

Pertussis is currently ranked fifth in global mortality among vaccine-preventable paediatric infections with cases on the rise over the last 30 years, despite global vaccination programs dating back to the 1940s. To better protect against this disease, the biology and physiology of Bordetella pertussis require a better understanding. This includes investigating the variability of B. pertussis growth.
This thesis will follow the growth dynamics of B. pertussis in several different strains. The growth of B. pertussis in vivo during colonisation, in vitro during phenotypic modulation, and in response to the antibiotic ampicillin will be explored.
The PMA-qPCR assay was successfully optimised for B. pertussis and allowed the growth of B. pertussis in vivo to be evaluated during the human colonisation study, while reporter constructs specific to each Bvg phase enabled the sensitivity to modulation during growth in vitro to be investigated amongst different strains of B. pertussis. Finally, growth of B. pertussis in the presence of ampicillin in vitro, in broth cultures, was determined and the mechanisms of resistance were investigated. Despite encountering some growth limitations, the results strongly suggest that an increase in the expression of genes encoding for penicillin binding proteins may contribute to ampicillin resistance.
Taken together, the variability of B. pertussis growth was observed utilising a variety of tools, in vivo and in vitro, allowing for a greater appreciation of the biology of this pathogen. This work highlights the importance of studying the growth of B. pertussis to better understand how to protect against pertussis infections and supports the determination of new treatment options and methods of prevention to help combat resurgence.

Date of Award	28 Apr 2021
Original language	English
Awarding Institution	University of Bath
Supervisor	Andrew Preston (Supervisor)