Formate-tetrahydrofolate ligase is involved in the virulence of Streptococcus suis serotype 2

• The role of formate-tetrahydrofolate ligase in the virulence potential of Streptococcus suis 2 was investigated.
• The virulence of Δfhs was significantly attenuated in mice.
• The Δfhs mutant exhibited reduced ability to colonize various tissues in piglets.

Streptococcus suis is an emerging zoonotic pathogen that causes severe infections in pigs and humans. However, the pathogenesis of S. suis remains unclear. The present study targeted a putative virulence-associated factor (fhs, encoding the formate-tetrahydrofolate ligase) of S. suis. To investigate the role of fhs in the virulence potential of S. suis serotype 2, an fhs deletion mutant (Δfhs) and the corresponding complementation strain (CΔfhs) were generated. The Δfhs mutant displayed similar growth compared to that of the wild-type and complementation strains. Using murine and pig infection models, we demonstrated for the first time that the formate-tetrahydrofolate ligase is required for the full virulence of S. suis 2. Our findings provide a new insight into the pathogenesis of S. suis 2.