Uncovering a cryptic Streptococcus suis endemic post-outbreak: Evidence of host switching to humans

Streptococcus suis (S. suis) is a neglected and emerging pathogen that leads to severe economic losses in swine industry. Despite its epidemic potential, the zoonotic threat posed by S. suis remains underappreciated, even after the unprecedented Sichuan outbreak, which highlighted its ability to cause fatal human infections. Understanding of the dynamics and evolution of this pathogen in human populations is crucial for preventing future outbreaks. Our study revealed the emergence of highly pathogenic S. suis lineages in Zhejiang Province following the Sichuan outbreak, showing an increasingly specialized lifestyle that has persisted for nearly two decades. Phylogenetic analysis traced the zoonotic transmission of this pathogen back to a livestock lineage in the Netherlands prior to 1990, which eventually led to the Sichuan outbreak lineage in 2005 and its subsequent spread to Zhejiang the same year. Two independent evolved sub-lineages were identified in Zhejiang, suggesting a cryptic, regional endemicity following the Sichuan outbreak. Furthermore, the accumulation of lineage-specific resistance and metabolic acclimation after divergence from the Sichuan population suggested potential regional evolutionary shifts in S. suis. These new findings could help inform future intervention strategies and guide public health policies.