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

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2017
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Massey University
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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.
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Enteritis, Salmonella enteritidis, Campylobacter jejuni, Genetics, Evolution, Research Subject Categories::NATURAL SCIENCES::Biology::Organism biology::Microbiology
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