The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis

Abstract

Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA-deleted mutant strain ΔsntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔsntA. The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of ΔsntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2′,3′-cyclic nucleotide 2′-phosphodiesterase/3′-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.

Porcine Beta-Defensin 2 Provides Protection Against Bacterial Infection by a Direct Bactericidal Activity and Alleviates Inflammation via Interference With the TLR4/NF-κB Pathway

“…Animal experiments were approved by the Laboratory Animal Monitoring Committee of Huazhong Agricultural University and performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Hubei Province, China (53).…”

ErpY-like lipoprotein of Leptospira outsmart host complement regulation by acquiring complement regulators, activating alternate pathway, and intervening membrane attack complex

“…By amassing host FH & FI, the rErpY-like protein restricts MAC deposition during the complement activation. Specific outer-membrane proteins of pathogenic bacteria, including streptococcal PepO and SntA (45,70), have been demonstrated to act as a double edge weapon where it can activate specific pathways of the complement to deplete the complement resources and also thwart the formation of the MAC on the pathogen's surface (45,70). Like the ErpY-like lipoprotein, these streptococcal proteins also intervene in the complement activation on the bacterial surface by interacting with the regulatory components of the complement system.…”

“…Among other bacterial species, inhibition of the CP has been recounted in the presence of PepO & SntA from Streptococcus spp. that can interact with C1q (45,70). Unlike others, CspA of B. burgdorferi exercises an inhibitory impact on the complement cascade by binding FH and C7 of the alternate and CP, respectively (74).…”

Molecular Dissection of Escherichia coli CpdB: Roles of the N Domain in Catalysis and Phosphate Inhibition, and of the C Domain in Substrate Specificity and Adenosine Inhibition

“…On the one hand, it plays in the economy of phosphate through the scavenging of nucleotidic derivatives like 2′,3′-cyclic mononucleotides and their 3′-nucleotide hydrolytic products, compounds of uncertain origin except by the possibility that they are formed by ribonuclease degradation of extracytoplasmic RNA [ 8 , 9 , 10 ]. On the other hand, there is consistent evidence for a role in virulence of the cpdB gene of gram-negative bacteria encoding periplasmic enzyme [ 11 , 12 ], and of a cpdB -like gene of gram-positive bacteria, encoding cell wall-anchored enzyme, and named sntA in Streptococcus suis or cdnP in S. agalactiae [ 7 , 13 , 14 , 15 , 16 , 17 ]. One should also be aware of the occurrence of another pro-virulent cyclic nucleotide phosphodiesterase of Mycobacterium tuberculosis , a DHH-DHHA1 domain protein encoded by the Rv2837c gene and named CdnP, although it is not homologous to S. agalactiae CdnP or to E. coli CpdB, and its outward/inward orientation in M. tuberculosis membrane is unclear [ 18 , 19 , 20 ].…”