Population genomics to inform control strategies for diverse bacterial pathogens

: (Alternative Format Thesis)

Abstract

Understanding diversity of bacterial populations at the lineage level can offer insight into the success of pathogenic species and their potential to diversify to occupy new niches. This can be implemented in the design of control strategies such as bespoke vaccines to reduce levels of infection in diverse environmental species such as, Campylobacter. Vaccines are the best method of control for bacteria and are effective against monomorphic organisms sharing similar antigenic variation. However, challenges arise in vaccine design for diverse, multi-niche species due to 1) high diversity of antigen variation and, 2) high evolvability of lineages, making serotype replacement likely. This dissertation describes a novel approach to estimate empirical rates of molecular evolution in Campylobacter species using closely related pairs of isolates and applies these rates, along with population genomics and a coalescent approach analogous with the well-known statistical birthday problem to understand diversity of lineages in the wild over short evolutionary timescales. The same methodology was applied to multiple pathogenic bacterial species with different transmission ecologies. Finally, this information, along with genomic methods, was used to inform the design and manufacture of an autogenous poultry vaccine to control Campylobacter levels entering retail and predict the long-term effects over time. Novel synonymous rates of molecular change (molecular clock) were estimated for C. coli and C. jejuni and the effects of horizontal gene transfer assessed to reveal high rates of recombination. Total rates of nucleotide change were also estimated and used alongside comparative genomics approaches to reveal the high maintenance of successful C. jejuni ancestral lineages over time along with recent rapid diversification of C. coli lineages. These results indicate that a vaccine targeting Campylobacter lineages would quickly be replaced by non-vaccine-specific lineages. The use of bioinformatics and increased availability of whole genome sequences has opened up an area of research where new options for disease control, along with the processes that underpin adaptation, can be explored.

Date of Award	17 Jan 2022
Original language	English
Awarding Institution	University of Bath
Supervisor	Samuel Sheppard (Supervisor) & Edward Feil (Supervisor)