Abstract
Streptococcus uberis is a leading cause of bovine mastitis, resulting in large economic losses and welfare issues for affected cows. However, relatively little is known about the global distribution and emergence of bovine mastitis-causing lineages and dissemination of antimicrobial resistance or virulence genes in the species. Here, we present a global framework for S. uberis based on whole-genome sequencing data from isolates across four continents (n=1,070). Internationally, S. uberis isolates show extensive genetic heterogeneity driven by homologous recombination and high levels of accessory genome content. Within the population, 35% (n=374/1,070) of isolates had at least one acquired antimicrobial resistance gene, while 59% (n=631/1,070) of isolates harboured a mutation in the penicillin-binding proteins (pbp2b or pbp2x) associated with decreased penicillin susceptibility, the front-line antimicrobial for mastitis infections. All described S. uberis virulence factors and currently proposed vaccine candidates were investigated for carriage and sequence heterogeneity to guide potential vaccine development, with two vaccine candidates (GapC and Sua) and seven putative virulence proteins (Fba, FbpS, Vru, GlnA, SUB0888, SUB0241 and haemolysin-like protein) having low naturally occurring sequence variation and high (>99%) coverage. This study will facilitate improved genomic surveillance for the emergence of antimicrobial resistance and virulence in this important mastitis pathogen.