Identification and characterization of ugpE required for the full virulence of Streptococcus suis

Streptococcus suis ( S. suis ) is an emerging zoonotic pathogen that threatens both animal and human health worldwide. UgpE is a protein subunit of the Ugp ( u ptake of g lycerol p hosphate) transporter system that is involved in glycerophospholipid synthesis in bacterial membranes. In this study, an ugpE deletion mutant was constructed and the effects of ugpE deletion on cell morphology, biofilm formation, and virulence were investigated. Deletion of ugpE did not affect bacterial growth but impaired cell chain formation and capsular synthesis by downregulating the mRNA levels of the capsular regulon genes cps-2B , cps-2C , and cps-2S . Deletion of ugpE also led to decreased tolerance to heat, oxidative, and acid-base stress. Crystal violet staining and scanning electron microscopy demonstrated ugpE negatively regulated biofilm formation in liquid culture and the rdar biofilm morphotype on agar plates. Moreover, ugpE deletion not only reduced hemolysin activity, survival in whole human blood, and anti-phagocytosis ability against porcine alveolar macrophages (PAM) but also enhanced bacterial adhesion and invasion of human cerebral microvascular endothelial cells (hCMEC/D3) by upregulating the expression of multiple genes associated with cell adhesion. In a mouse infection model, ugpE deletion significantly attenuated virulence and lowered the number of viable bacteria in the blood and major organs, as well as distribution of macrophages. In conclusion, this study identified UgpE as a novel virulence factor that plays a pivotal role in the regulation of virulence and biofilm formation of S. suis .