Regulative synthesis of capsular polysaccharides in the pathogenesis of Streptococcus suis

Streptococcus suis (S. suis) is an important zoonotic pathogen causing substantial economic losses in the swine industry. S. suis serotype 2 (SS2) is often isolated from the diseased. S. suis expresses capsular polysaccharide (CPS), a virulence factor crucial for their survival in the blood. However, the role of CPS in the pathogenesis of S. suis is incomplete. Here, we showed a dynamic regulation of CPS in S. suis pathogenesis. In a mouse infection model, an SS2 strain (05ZYH33) was detected in the nasal-associated lymphoid tissue (NALT) and cerebrospinal fluid (CSF) as early as 30 min after intranasal inoculation without bacteremia. Histological analysis revealed that 05ZYH33 in the nasal cavity invaded the olfactory epithelium, resulting in early brain inflammation. Transmission electron microscopy showed that 05ZYH33 isolated from NALT and CSF at early infection time had a thin layer of CPS, and those detected in the blood 5 h post- inoculation showed a much thicker CPS. In addition, adoptive transfer of anti-CPS restricted 05ZYH33 in the blood but not in NALT or CSF. However, an antiserum directed to multiple non-CPS virulence factors (anti-V5) efficiently inhibited 05ZYH33 in NALT, CSF, and blood. Thus, 05ZYH33 colonizes NALT more efficiently without CPS and subsequently invades the meninges through the olfactory nerve system. These findings provide valuable information for the treatment of S. suis infection and the development of vaccines across serotypes of S. suis by targeting CPS-independent immunity.