Genomic epidemiology of the livestock pathogen Streptococcus uberis

Despite widespread attempts to control intramammary infections (IMI) caused by Streptococcus uberis, it remains one of the most frequent causative agents of bovine mastitis across the UK and globally. S. uberis is found commensally colonising cattle and ubiquitously in the farm environment, and whilst typically considered to be an opportunistic pathogen, the multi-niche lifestyle of this bacterial species is poorly understood. Elucidating the evolutionary dynamics of a bacterial species or population is essential in order to investigate their epidemiology and inform control strategies; as such, this thesis utilises a global collection of S. uberis whole-genome sequences to carry out an array of population genomic analyses, providing high-resolution insight into the evolution and adaptation of S. uberis. Multiple approaches were used to stratify the population structure of S. uberis isolates collected from several host species and disease types. A high degree of both within- and between-strain diversity was observed, despite the presence of a tightly conserved species boundary, suggesting that population-wide heterogeneity is an adaptive advantage for the lifestyle of S. uberis. Allelic variation within core genes, rather than gene content differences, underpinned the population and genomic diversity observed, facilitated by frequent micro-recombination events. Next, virulence-associated factors that may contribute to the survival and success of S. uberis in multiple host- and environmental-associated niches were investigated. Amongst the global S. uberis dataset, isolates were found to encode a conserved array of virulence-associated factors, including an expansive repertoire of cell wall anchored proteins and glycoproteins. Additionally, novel virulence-associated factors, such as putative pilus- and capsular polysaccharide-encoding loci, are reported for the first time in this species. The cell wall anchored proteins SclB and Lbp were encoded within genomic recombination ‘hotspots’, likely mediating antigenic variation. S. uberis was found to encode a complete set of highly conserved comRS machinery which may facilitate genetic competence in this species. Lastly, the genomic landscape of S. uberis isolated from bovine mastitis cases in Scotland was explored, providing valuable contributions to current S. uberis disease surveillance efforts, both on-farm and on a national scale. MLST was demonstrated to lack the genomic resolution required for the investigation of S. uberis transmission events and outbreaks, with core genome SNP distances (cgSNPs) the most appropriate typing tool for this context. The detection of closely related (<100 cgSNPs) but spatially and temporally distinct isolates disrupts the common presumption that closely related isolates are a result of contagious transmission, and the need to re-define “contagious” and “environmental” when classifying S. uberis isolates or transmission routes was highlighted. Overall, these findings reveal that the highly heterogeneous population structure of S. uberis is likely an adaptive advantage to the multi-niche lifestyle of this species, facilitated by frequent recombination events. The results presented provide valuable insights into the evolutionary processes shaping the S. uberis population structure, and help to inform control strategies for infections caused by S. uberis.