Bacterial genomics and its applications in molecular epidemiology of Salmonella enterica serovar Typhimurium

Salmonella enterica serovar Typhimurium (or simply referred to as Typhimurium) is a food- and water-borne pathogen, which is one of the most common cause of enteric disease in both humans and animals worldwide. Current epidemiological surveillance of Typhimurium relies on phage typing. Phage typing has been found to be particularly useful for tracking the spatio-temporal distribution of antibiotic resistance strains, for example DT204c in the 1970s and the currently epidemic strains of phage type DT104. However, knowledge of the evolutionary relationships between phage types; the genetic basis for the variation in phage sensitivity remains; as well as temporal dominance and the host adaptation of particular Typhimurium phage types remain largely unknown. To address these questions the thesis first aimed to utilise single nucleotide polymorphisms (SNPs) based on a previous study and comparison of published genome strains for establishing the evolutionary relationships of a diverse collection of Typhimurium strains with various phage types. The results suggested that phage typing may not be useful for long-term epidemiological studies as different phage types may have arisen independently multiple times. However, strains with multiple phage types were grouped together, suggesting that SNP typing still had a limited discriminatory power. To resolve this, other molecular markers, variable number of tandem repeats (VNTRs) were applied to the same collection of strains. Multilocus VNTR analysis (MLVA) was highly discriminating but the phylogenetic signals between strains were not apparent. Therefore, a combination of SNP typing and MLVA is required for local and global epidemiology and the evolutionary analysis of Typhimurium. Lastly, six diverse Typhimurium strains based on previous SNP typing study were investigated at genome level using high-throughput sequencing, to determine genetic variations that may contribute to their prevalence and host-adaptations. The genome data were compared to seven other genomes publicly available. Genomic information obtained from this study has shown that Typhimurium is still evolving. Genetic diversity within Typhimurium is mainly due to accumulation of SNPs. Altogether, this study has provided a better insight into the evolution and genetic diversity between different Typhimurium phage types