# Global emergence and evolution of Staphylococcus aureus clonal complex 59

## TL;DR

This study explores the global spread and evolution of a dangerous type of Staphylococcus aureus called CC59, focusing on its adaptation and transmission patterns in Asia.

## Contribution

The study provides a genomic epidemiology framework for CC59 and identifies virulence targets through lineage analysis and functional experiments.

## Key findings

- CC59 has three distinct lineages with region-specific origins in the USA, Australia, and China.
- Respiratory tract colonization in China-associated CC59 strains acts as a dissemination hub for bloodstream infections.
- Clf-Sdr family proteins are enriched in human isolates and linked to biofilm formation in virulent CC59 strains.

## Abstract

Staphylococcus aureus clonal complex 59 (CC59) has emerged as a significant public health threat in Asia, yet the mechanisms driving its host adaptation and global evolutionary success remain poorly understood. Here, we performed a comprehensive genomic analysis of 3,994 global CC59 isolates, which included 549 isolates associated with bloodstream infections from China. Our analysis revealed three phylogenetically distinct lineages exhibiting region-specific distribution patterns, tracing their origins to the USA, Australia, and China. Notably, high-risk CC59 clones circulating in Taiwan likely diverged from mainland Chinese strains during the 1940s-1960s, coinciding with historical population migration following the Chinese civil war around 1949. Among China-associated CC59 strains, respiratory tract colonization was related to high cross-source linkage across multiple ecological niches, suggesting its role as a dissemination hub, particularly for bloodstream infection (BSI). Additionally, we observed significant enrichment of Clf-Sdr family proteins in human isolates, especially in BSI cases. Functional characterization using ΔclfB and ΔsdrD knockout strains demonstrated impaired biofilm formation, recapitulating findings in USA300. These findings establish an evolutionary framework for CC59 surveillance and highlight promising potential targets for anti-virulence therapeutics.

The prevalence and propagation of Staphylococcus aureus clonal complex 59 (CC59) in Asia are serious public health concerns. To understand its adaptation to hosts and worldwide evolutionary success, we analyzed the genomic population structure of all CC59 isolates and traced their evolutionary history. Our research indicates that CC59 lineages developed through unique evolutionary routes that vary across time and space, highlighting their adaptation to diverse ecological environments. This study presents a comprehensive genomic epidemiology framework that integrates extensive metadata analysis with evolutionary assessment. It serves as a model for future S. aureus monitoring and provides insights into potential targets for interventions focused on reducing virulence.