Proteomics identification of novel fibrinogen-binding proteins of Streptococcus suis contributing to antiphagocytosis

Abstract

Streptococcus suis serotype 2 (SS2) induced sepsis and meningitis are often accompanied by bacteremia. However, the mechanism whereby it helps S. suis to evade PMN-mediated phagocytosis remain unclear. Because of the central roles of bacteria-human fibrinogen (hFg) interaction in innate immunity, here, a proteomics based Far-western blotting (PBFWB) was developed to identify the fibrinogen-binding surface proteins of S. suis (SsFBPs) on a large-scale. And then thirteen potential SsFBPs were identified by PBFWB and we selected seven potential surface proteins to further confirm their binding ability to hFg, of which the gene mutant strains of MRP displayed significantly decrease in binding to immobilized hFg. Additionally, the polyclonal antibodies against Enolase were found to significantly inhibit the binding of SS2 to hFg. Strikingly, MRP and Enolase were found to improve the antiphagocytic ability of SS2 to PMNs by interacting with hFg and enhance the survival of SS2 in human blood. Taken together, the PBFWB method provides useful clues to the bacteria-host interactions. These studies firstly disclose MRP and Enolase were involved in immune evasion of SS2 at least in part by binding to Fg, which make them potential targets for therapies for SS2 infection.

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

“…Moreover, in Vietnam and Thailand, S. suis has been identified as the first and second most common cause of adult meningitis, respectively [5]. S. suis deploys a plethora of mechanisms to evade innate and adaptive immune responses: among the various virulence factors described for S. suis , the CPS plays essential roles in resistance to phagocytosis by several innate immune cells [6,7]; the suilysin and the cell wall also contribute to limiting complement-dependent clearance by dendritic cells [7]; S. suis produces several immunoglobulin degrading enzymes contributing to immune escape during infection including IgA1 protease, porcine IgM-specific protease Ide Ssuis , and porcine IgG-specific protease IgdE [8–10]; S. suis exploits several surface proteins and transcriptional regulators to resist killing by neutrophils, including MRP and Enolase [11], NisKR [12], CcpA [13]. …”

The non-conserved region of MRP is involved in the virulence ofStreptococcus suisserotype 2

“…6,7 A recent study also indicated that MRP was a major fibrinogen-binding protein. 8 The binding of MRP with human fibrinogen increases the viability of SS2 in human blood and promotes the development of SS2 meningitis. 8,9 However, in North America, a MRP-strain was shown to be virulent, while a MRPC strain was reported to be avirulent.…”

Processed Food Additive Microbial Transglutaminase and Its Cross-Linked Gliadin Complexes Are Potential Public Health Concerns in Celiac Disease

“…It is the correct place to emphasize that mTG/tTG isopeptide-bonds are incredibly resistant to luminal proteases, reducing agents, detergents, bile acids, immunoglobulins, and other antimicrobial molecules [13,25,78,79]. Secondly, Streptococcus suis mTG was described recently to exert antiphagocytic activity, thereby compromising a powerful and indispensable immune protective mechanism [26,80,81]. The same Streptococcus suis can evade neutrophils by preventing neutrophil extracellular trap formation.…”