Abstract
Streptococcus suis serotype 2 (Ss2) is an important swine and human zoonotic pathogen. In the present study, we identified a novel secreted immunogenic protein, SsTGase, containing a highly conserved eukaryotic-like transglutaminase (TGase) domain at the N terminus. We found that inactivation of SsTGase significantly reduced the virulence of Ss2 in a pig infection model and impaired its antiphagocytosis in human blood. We further solved the crystal structure of the N-terminal portion of the protein in homodimer form at 2.1 Å. Structure-based mutagenesis and biochemical studies suggested that disruption of the homodimer directly resulted in the loss of its TGase activity and antiphagocytic ability. Characterization of SsTGase as a novel virulence factor of Ss2 by acting as a TGase would be beneficial for developing new therapeutic agents against Ss2 infections.
Highlights
SsTGase was a newly identified secreted immunogenic protein of S. suis 2
We identified that SsTGase was secreted by suis serotype 2 (Ss2) through Western blotting despite the fact it contained a predicted transmembrane segment (Fig. 1, A and B)
The results from the Polymorphonuclear Leukocyte (PMN) killing assay suggested that the survival rates of the ⌬SsTGase strain were much lower than those of the wild-type strain 05ZYH33 (WT) and C⌬SsTGase strains by 1–3 h (Fig. 1C)
Summary
SsTGase was a newly identified secreted immunogenic protein of S. suis 2. We identified a novel secreted immunogenic protein, SsTGase, containing a highly conserved eukaryotic-like transglutaminase (TGase) domain at the N terminus. The TGase domain belongs to the TGase-like superfamily (PF01841 in the PFAM database) [11], which contains a highly conserved catalytic triad Cys302-His333Asp348 We named this protein as SsTGase in Ss2. Structure-based mutagenesis and biochemical studies suggested that dimerization of the protein was critical for its activation and antiphagocytic ability.
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