Abstract
Staphylococcus aureus is a major zoonotic bacterial pathogen that causes a broad spectrum of human and animal diseases, including skin infections, sepsis, endocarditis, and bovine mastitis. In the geographically isolated setting of New Zealand, the population structure of S. aureus exhibits a distinct genomic profile. Globally, bovine S. aureus isolates are primarily associated with sequence types (STs), ST97 and ST151, whereas in New Zealand, ST1 predominates, accounting for approximately 70% of bovine isolates. ST1 is also a clinically significant sequence type in humans. This study employed a comparative One Health approach to investigate genetic differences in 520 S. aureus ST1 isolated from bovine milk and human clinical samples. We aimed to explore genomic features associated with persistence and diversification across hosts, focusing on antimicrobial resistance (AMR), virulence, and mobile genetic elements. Comparative genomics revealed that human isolates carried a significantly higher burden of AMR genes, consistent with clinical selective pressure. In contrast, 83% of bovine isolates harbored a prophage (φSabovST1) similar to S. aureus prophage φSaov3. This prophage encodes bovine-adapted leukocidins (LukMF’), supporting host-specific adaptation. Phylogenetic analysis revealed long branches, suggesting insufficient sampling, highlighting the need for broader genomic surveillance to resolve evolutionary relationships and transmission dynamics of S. aureus ST1 in New Zealand. These findings highlight the complex history of host interactions, historical transmission events, and ongoing bacterial adaptation. Expanding sampling efforts across human, animal, and environmental reservoirs will provide deeper insights into strain diversity, elucidate transmission pathways, and inform strategies to mitigate zoonotic risks.IMPORTANCEThis study presents a comprehensive genomic analysis of S. aureus ST1, a lineage that is unusually dominant in both bovine and human populations in New Zealand. Leveraging New Zealand’s geographical isolation, we provide critical insights into the persistence, diversification, and adaptation of S. aureus, offering valuable knowledge to advance disease prevention in both public and veterinary health and strengthening global biosecurity. The development of the first bovine ST1 reference genome serves as a valuable resource for future research, while the identification of a novel prophage (φSabovST1) carrying bovine-specific leukocidins underscores the role of mobile genetic elements in host specificity and virulence. Human isolates exhibited a higher prevalence of antimicrobial resistance genes. Phylogenetic analysis further revealed two main circulating clades of ST1 with interspersed host origins, highlighting the critical need for integrated One Health approaches to more effectively monitor and manage zoonotic pathogens across agricultural and public health systems.