Transmission and evolution of bacteria during the course of enteritis outbreaks : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy, Massey University, Palmerston North, New Zealand
Bacterial enteritis outbreaks are a worldwide problem. They are hard to investigate as the bacterial agents
are often associated with multiple sources, closely-related bacteria often co-colonise these sources, highly
discriminatory tests are often required to distinguish between these bacteria, and bacteria are continuously
evolving, changing how they behave. In this thesis I investigated the transmission and evolution of bacteria
over the course of enteritis outbreaks by integrating genomic, phenotypic and antibiotic susceptibility testing,
and phylogenetic modelling in four studies.
The aim of the first study was to investigate the origin, evolution and transmission of Salmonella enterica
serovar Typhimurium DT160 over a 14-year long outbreak in New Zealand. Genomic analysis of 109 DT160
isolates collected over this timeframe established that the DT160 strain was introduced into New Zealand
approximately a year before the first human isolate was reported; there were frequent transmissions between
the source groups investigated (human, wild bird, poultry and bovine); and there was no evidence of specific
selective pressures imposed on DT160. This study demonstrated how genomic analyses can be used to
investigate extended outbreaks of bacterial diseases.
The aim of the second study was to investigate whether two ancestral state reconstruction models (the
discrete trait analysis and structured coalescent models) were applicable to salmonellosis outbreak investiga-
tions. Both models were used to estimate transmission and population parameters of simulated salmonellosis
outbreaks. Comparisons between the models' estimates and the true transmission and population values for
the simulations revealed that both models made assumptions that did not apply to outbreaks and prevented
them from accurately predicting these parameters. This study highlighted the need for outbreak-specific
phylogenetic transmission models.
The aim of the third study was to investigate the relationship between two strains of Salmonella that
were the predominant causes of human salmonellosis in New Zealand in the 2000s (S. Typhimurium DT160
and S. Typhimurium DT56 variant), and identify potential reasons for one strain declining (DT160) as the
other emerged (DT56 variant). This study demonstrated how genomic analyses can be used to compare
Salmonella strains and identify genetic elements that may in
uence strain behaviour.
The aim of the fourth study was to investigate a patient that had presented excreting the same genotype
of Campylobacter, C. jejuni ST45, on multiple occasions over a 10-year period. Genomic analyses, pheno-
typic testing and antimicrobial susceptibility testing of sixteen Campylobacter isolates collected from the
patient found that the patient was persistently colonised with Campylobacter over this period, and that the
Campylobacter had adapted to long-term colonisation by altering its motily and developing resistance to the
antibiotics the patient had been prescribed. This study demonstrated how genomic analyses can be used to
investigate a patient's infection history.
These studies demonstrated the applicability and limitations of genomic analyses when investigating
bacterial enteritis outbreaks, how genetics and the environment in
uence bacterial evolution, and highlighted
areas in the fields of microbiology, phylogenetics, epidemiology and public health that require further research.