Streptococcus Suis Serotype 2 Strains Research Articles

Promising potential of machine learning-assisted MALDI-TOF MS as an effective detector for Streptococcus suis serotype 2 and virulence thereof.

To the best of our knowledge, this study reveals a strong correlation between mass spectra pattern and virulence phenotype among S. suis for the first time. In order to make the findings applicable and to excavate the intrinsic information in the spectra, the classifiers based on the machine learning algorithms were established, and RF (Random Forest)-based models have achieved an accuracy of over 90%. Overall, this study will pave the way for virulent SS2 (Streptococcus suis serotype 2) rapid detection, and the important findings on the association between genotype and mass spectrum may provide a new idea for the genotype-dependent detection of specific pathogens.

Thioredoxin A of Streptococcus suis Serotype 2 Contributes to Virulence by Inhibiting the Expression of Pentraxin 3 to Promote Survival Within Macrophages.

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein of 104 amino acids with a canonical CGPC active motif and an identity 70-85% similar to the thioredoxin A (TrxA) in other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress, as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2 and paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7 cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin 3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant strain is far more easily cleared from the body than the wild type strain in the period from 8-24h, and exhibits significantly attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection.

Streptococcus suis serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for large economic losses in pig production and a great threat to human health. Pentraxin 3 (PTX3) is an essential regulator of the innate immune response to bacterial pathogens; however, its role during SS2 infection is not fully understood. In this study, we found that the SS2 strain HA9801 induced a significant inflammatory response in the mouse air pouch model; this response was amplified by the treatment of exogenous PTX3 simultaneously in terms of the results of inflammatory cell recruitment and proinflammatory cytokine IL-6 production. In addition, PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801. The supplementation of exogenous PTX3 significantly reduced the bacterial loads in a dose-dependent manner in lungs, livers and bloods of SS2-infected mice compared to the samples with HA9801 infection alone; this finding indicated that PTX3 may facilitate the bacterial clearance through enhancing the host inflammatory response during SS2 infection. Both PTX3 and SS2 capsular polysaccharide (CPS2) were required for the robust inflammatory response, implying that the host PTX3 protein and SS2 surface CPS2 modulate the host innate immune response in concert. All of these results suggested that PTX3 is a potential novel biological agent for the SS2 infection; however, the recommended dose of PTX3 must be evaluated strictly to avoid inducing an excessive inflammatory response that can cause serious tissue injury and animal death.

Extraction and reverse transcription of total rna from mouse brain-derived endothelial cells.3 infected by streptococcus Suis 2

Streptococcus suis 2 is an important emerging zoonotic pathogen. It mainly causes meningitis in pigs. We use SS2 to infect bEnd.3 to get stable cDNA for next research on differences in gene expression and protein expression of cytokines.
 The paper presents an SS2 study for bEnd.3 infection to obtain stable cDNA for subsequent study of differences in gene expression and cytokine protein expression.
 Objective: The aim of this study was to extract the total RNA from mouse brain-derived Endothelial cells (bEnd.3) infected by Streptococcus suis serotype 2 (SS2) and transcript to complementary DNA (cDNA).
 Materials and methods: SS2 strain were obtained from Jilin University, China. BEnd.3 was from Henan institute of Science of Technology, China. Reverse transcription kit was from Takara company, Japan. Trizol was from Bioteke company,China. Nanodrop instrument was from Thermo company, USA. Polymerase chain reaction (PCR) instrument was from Biometra company, Germany.
 We used SS2 to infect bEnd.3 at a multiplicity of infection (MOI) of 100 for 12h. Cells were harvested and Trizol method was chose to extract the total RNA of bEnd.3 infected by SS2. Nanodrop instrument was used to measure the concentration of RNA and the values of OD260/280 and OD260/230. RNA were transcripted to cDNA with reverse transcription kit by PCR instrument.
 Results: trizol method used in this study was reliable and high-quality RNA were obtained. Stable cDNA were obtained by reverse transcription kit.
 Conclusion: in this experiment high-quality RNA was obtained and reverse transcribed to stable cDNA for subsequent detection of related cytokines. This study provides an approximate RNA extraction method and good experimental foundation for downstream research.

YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

ABSTRACT The Streptococcus suis serotype 2 (SS2) is a significant zoonotic pathogen that is responsible for various swine diseases, even causing cytokine storms of Streptococcal toxic shock-like syndromes amongst human. Cell wall anchoring proteins with a C-terminal LPxTG are considered to play vital roles during SS2 infection; however, their exporting mechanism across cytoplasmic membranes has remained vague. This study found that YSIRK-G/S was involved in the exportation of LPxTG-anchoring virulence factors MRP and SspA in virulent SS2 strain ZY05719. The whole-genome analysis indicated that diverse LPxTG proteins fused with an N-terminal YSIRK-G/S motif are encoded in strain ZY05719. Two novel LPxTG proteins SspB and YzpA were verified to be exported via a putative transport system that was dependent on the YSIRK-G/S directed translocation, and portrayed vital functions during the infection of SS2 strain ZY05719. Instead of exhibiting an inactivation of C5a peptidase in SspB, another LPxTG protein with an N-terminal YSIRK-G/S motif from Streptococcus agalactiae was depicted to cleave the C5a component of the host complement. The consequent domain-architecture retrieval determined more than 10,000 SspB/YzpA like proteins that are extensively distributed in the Gram-positive bacteria, and most of them harbor diverse glycosyl hydrolase or peptidase domains within their middle regions, thus presenting their capability to interact with host cells. The said findings provide compelling evidence that LPxTG proteins with an N-terminal YSIRK-G/S motif are polymorphic effectors secreted by Gram-positive bacteria, which can be further proposed to define as cell wall anchoring effectors in a new subset.

In vitro expression of enolase from Streptococcus suis serotype 2 and its antigenicity

Streptococcus suis serotype 2(SS2) is one of the most important pathogens in the porcine industry and an important zoonotic agent. The absence of suitable vaccine or virulence markers makes SS2 infections more difficult to control. An immunoproteomics approach is used for identifying antigenic proteins in SS2 recognized enolase, which may represent strain-specific antigenic proteins and potential protective antigens. This study aims to clone, express enolase gene from SS2 and use western blotting to evaluate the antigenicity. Enolase gene from the SS2 strain was amplified with specific primers. The obtained PCR product was inserted into an expression vector, pGEX-4T1. The recombinant vector was then transformed into BL21 cells for protein expression. Subsequently, the immunological activity of the recombinant enolase was tested by western blotting with human sera in the convalescent phase. The glutathione S-transferase (GST)-tag fusion enolase was purified by glutathione sepharose affinity chromatography for further studies. The SS2 recombinant enolase was successfully expressed in E. coli. The western blotting analysis demonstrated that enolase has an antigenic property, which is recognized by patients naturally infected with SS2.

SBP1 is an adhesion-associated factor without the involvement of virulence in Streptococcus suis serotype 2

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that infects swine and humans with high mortality and morbidity. Although a number of virulence-associated factors have been reported, the understanding of the molecular mechanism underlying SS2 pathogenicity remains limited. Our previous studies revealed that srtBCD-associated protein 2’ (SBP2′) contributed to the pathogenesis of SS2, but the function of another member in the srtBCD cluster, srtBCD-associated protein 1 (SBP1) was still unknown. Here, we found that sbp1 was widely distributed among high virulent SS2 strains, suggesting that sbp1 may be involved in the pathogenesis of SS2. To investigate the function of SBP1, we firstly conducted Western blotting analyses to confirm that SBP1 was expressed in the high virulent SS2 strain ZY05719 both in vivo and in vitro, then constructed the deletion mutant of sbp1 by homologous recombination. Bacterial adhesion assay, indirect immunofluorescence assay and protein binding assay all demonstrated that SBP1 was associated with adhesion of SS2 to HEp-2 cells. However, SBP1 did not influence the invasion, phagocytosis or intracellular survival of SS2. Furthermore, infection assays in vivo showed that inactivation of sbp1 failed to impair the ability of SS2 to cause zebrafish and mouse mortality. Overall, these results indicate that SBP1 is an adhesion-associated factor without the involvement of virulence in Streptococcus suis serotype 2.

Fibronectin-/fibrinogen-binding protein (FBPS) is not a critical virulence factor for the Streptococcus suis serotype 2 strain ZY05719

Fibronectin-/fibrinogen-binding protein (FBPS) of Streptococcus suis serotype 2 (SS2) is an atypical anchorless microbial surface components recognizing adhesive matrix molecules (MSCRAMM) for which the role in bacterial infection are not clearly established. To investigate the biological functions of FBPS, an fbps knockout mutant was constructed in SS2 strain ZY05719 to explore the phenotypic changes between the wild-type and mutant strains. Cell morphology analyses combined with the basic growth curves showed that deletion of fbps does not significantly influence neither the thickness of the capsule of SS2 nor the cell growth characteristic. In addition to three previously identified host components fibronectin (FN), factor H (FH) and fibrinogen (FG), we also found that both laminin (LN) and immunoglobulin G (IgG) could bind specifically to FBPS. Furthermore, we confirmed that FBPS play an important role in adherence of SS2 to host cells. The in vitro assays demonstrated that an inactivation of fbps does not inhibit the intracellular survival of SS2 in RAW246.7 macrophages, attenuate the ability of invasion of host cells or the growth ability in pig blood. Additionally, the fbps mutation failed to decrease the virulence of SS2 in both BALB/c mice and zebrafish. Finally, immunization with recombinant FBPS showed no significant difference from the control groups in terms of murine viability after SS2 challenge. Taken together, we concluded that FBPS is not a critical virulence factor for the SS2 strain ZY05719.

EGFR transactivation contributes to neuroinflammation in Streptococcus suis meningitis.

Background Streptococcus suis serotype 2 (SS2) is an important zoonotic bacterial pathogen in both humans and animals, which can cause high morbidity and mortality. Meningitis is one of the major clinical manifestations of SS2 infection. However, the specific process of SS2 meningitis and its molecular mechanisms remain unclear. Epidermal growth factor receptor (EGFR) has been reported to initiate transduction of intracellular signals and regulate host inflammatory responses. Whether and how EGFR contributes to the development of S. suis meningitis are currently unknown.MethodsThe tyrosine phosphorylation of cellular proteins, the transactivation of EGFR, as well as its dimerization, and the associated signal transduction pathways were investigated by immunoprecipitation and western blotting. Real-time quantitative PCR was used to investigate the transcriptional level of the ErbB family members, EGFR-related ligands, cytokines, and chemokines. The secretion of cytokines and chemokines in the serum and brain were detected by Q-Plex™ Chemiluminescent ELISA.ResultsWe found an important role of EGFR in SS2 strain SC19-induced meningitis. SC19 increasingly adhered to human brain microvascular endothelial cells (hBMEC) and caused inflammatory lesions in the brain tissues, with significant induction and secretion of proinflammatory cytokines and chemokines in the serum and brains. SC19 infection of hBMEC induced tyrosine phosphorylation of cellular EGFR in a ligand-dependent manner involving the EGF-like ligand HB-EGF, amphiregulin (AREG), and epiregulin (EREG) and led to heterodimerization of EGFR/ErbB3. The EGFR transactivation did not participate in SS2 strain SC19 adhesion of hBMEC, as well as in bacterial colonization in vivo. However, its transactivation contributed to the bacterial-induced neuroinflammation, via triggering the MAPK-ERK1/2 and NF-κB signaling pathways in hBMEC that promote the production of proinflammatory cytokines and chemokines.ConclusionsWe investigated for the first time the tyrosine phosphorylation of cellular proteins in response to SS2 strain SC19 infection of hBMEC and demonstrated the contribution of EGFR to SS2-induced neuroinflammation. These observations propose a novel mechanism involving EGFR in SS2-mediated inflammatory responses in the brain, and therefore, EGFR might be an important host target for further investigation and prevention of neuroinflammation caused by SS2 strains.

A novel virulence-associated protein, vapE, in Streptococcus suis serotype 2.

Streptococcus suis serotype 2 (SS2) is an important pathogen that affects pigs. However, neither its virulence nor its pathogenesis of infection has yet to be fully elucidated. The present study identifies a novel virulence‑associated protein E gene (vapE) of SS2. To investigate the importance of vapE in SS2 infection, a vapE knock‑out mutant based on SS2 wild‑type strain ZY458 was designated 458ΔvapE. 458ΔvapE was generated through homologous recombination, using a combined plasmid with a vapE knock‑out fragment and a pSET4s suicide vector. Additionally, the 458ΔvapE strain was transformed by a pAT18 shuttle plasmid containing the vapE gene. A functionally complemented strain for the vapE gene [termed 458ΔvapE (pvapE)] was constructed. Animal experiments demonstrated that mice infected with ZY458 and 458ΔvapE (pvapE) exhibited severe clinical symptoms, including depression, apathy, fever, anorexia, emaciation, swollen eyes and neural disorders, and died within two days of infection. All mice infected with ZY458, and 85% of mice infected with 458ΔvapE (pvapE), died within 2 days of infection. In contrast, mice inoculated with 458ΔvapE exhibited only mild clinical symptoms in the first 2 days following infection, and recovered within a week. A bacterial colonization assay demonstrated the ability of the 458ΔvapE mutant SS2 strain to colonize the heart, liver, spleen, lung and kidney of infected mice. PCR analysis of the vapE gene revealed that functional vapE was detected in virulent strains, but not in avirulent and carrier strains of S. suis SS2. These findings indicate that vapE is important for the pathogenesis of SS2.

Streptococcus suis serotype 2 strains can induce the formation of neutrophil extracellular traps and evade trapping.

Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, especially in people that come into close contact with pigs or pork products. Streptococcus suis serotype 2 (SS2) is considered to be the most pathogenic and prevalent capsular type. As a first line of immune defense against SS2 infection, neutrophils can eliminate the invader not only by phagocytosis but also by neutrophil extracellular traps (NETs)-mediated killing. SS2 can resist phagocytosis through polysaccharide capsule (CPS), but how this strain evades the effects of NETs remains to be determined. The present study demonstrated that the epidemic strain 05ZY, the highly pathogenic strain P1/7 and the intermediately pathogenic strain A7 could induce the formation of NETs. Furthermore, SS2 strains could successfully resist NETs-mediated killing, and the CPS structure contributed to this resistance by escaping the trapping. Therefore, the CPS structure not only contributed to the SS2 strains' resistance to phagocytosis-mediated killing but also played an essential role in evading NETs trapping and further killing in vitro. This study strengthens our understanding of how S. suis can evade innate immune surveillance and elimination.

The truncated major pilin subunit Sbp2 of the srtBCD pilus cluster still contributes to Streptococcus suis pathogenesis in the absence of pilus shaft.

Streptococcus suis serotype 2 (SS2) is an emerging zoonotic agent responsible for a number of infections in pigs and humans. Pili have been proposed as virulence factors in Gram-positive bacteria. However, due to the abolition of pili production, the function of the srtBCD pilus cluster, especially the truncated major pilin subunit Sbp2 (Sbp2', Sbp2″), has not been explored. In this study, isogenic mutants (Δsbp2', Δsbp2″) were constructed by homologous replacement in SS2 strain P1/7. Deletion of sbp2' attenuated the virulence in a zebrafish model as shown by more than an eightfold increase in the LD50 of Δsbp2', compared with that of the parent strain. In addition, the adhesion of Δsbp2' to HEp-2 cell monolayers decreased significantly. Compared with the parent strain, no obvious differences in virulence and adherence efficiency were observed for Δsbp2″. Our data suggest that Sbp2' could be involved in SS2 pathogenesis despite absence of its pilus shaft.

Characterization and Proteome Analysis of Inosine 5-Monophosphate Dehydrogenase in Epidemic Streptococcus suis Serotype 2

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe disease symptoms in pigs and humans. In the present study, we found one isogenic mutant lacking inosine 5-monophosphate dehydrogenase (IMPDH) ΔZY05719 was attenuated in pigs compared with the wild-type SS2 strain ZY05719. Comparative proteome analysis of the secreted proteins expression profiles between ZY05719 and ΔZY05719 allowed us to identify Triosephosphate isomerase (TPI) and glyceraldehyde phosphate dehydrogenase (GAPDH), which were down expressed in the absence of the IMPDH. Both of them are glycolytic enzymes participating in the glycolytic pathway. Compared with ZY05719, ΔZY05719 lost the ability of utilize mannose, which might relate to down expression of TPI and GAPDH. In addition, GAPDH is a well-known factor that involved in adhesion to host cells, and we demonstrated ability of adhesion to HEp-2 and PK15 by ΔZY05719 was significantly weakened, in contrast to ZY05719. The adhesion to host cells is the crucial step to cause infection for pathogen, and the reduction adhesion of ΔZY05719, to some extent illustrates the attenuated virulence of ΔZY05719.

Proteome Analysis of the Two-Component SalK/SalR System in Epidemic Streptococcus suis Serotype 2

Streptococcus suis serotype 2 (SS2) is a major swine pathogen of significant commercial importance worldwide and an emerging zoonotic agent of human streptococcal toxic shock-like syndrome. We previously reported that the Chinese highly pathogenic SS2 strains specifically harbor an 89K pathogenicity island, and the SalK/SalR two-component system encoded within this island mediates a piglet-lethal phenotype. However, its regulatory mechanism remains obscure. In the present study, we performed a proteome analysis to identify the target proteins regulated by the SalK/SalR system. This expression profiling analysis reveals 14 down-regulated proteins and 1 up-regulated protein. In partial accord with our previous microarray analysis, 9 out of the 14 down-regulated genes are also repressed at the transcriptional level. From the 9 matched genes, 5 were selected and further subjected to gene knockout and experimental infection of mice. The results show that the selected 5 genes are potential virulence factors and participate to various extents in the pathogenesis of SS2 infection, and may contribute to the attenuation of virulence mediated by the SalK/SalR system.

Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays

BackgroundOur previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays.ResultsOur results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution.ConclusionsOur deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.

Induction of protective immune response against Streptococcus suis serotype 2 infection by the surface antigen HP0245

Streptococcus suis serotype 2 (SS2) is an emerging zoonotic pathogen. Prevention and control of the diseases caused by SS2 bacteria are hampered by the lack of effective vaccines. We report that an in vivo-induced protein HP0245 was located at the cell surface of SS2. The extracellular peptide of HP0245 was produced in Escherichia coli BL21 (DE3). Its immunogenicity was compared with SS2 bacterin. Like SS2 bacterin, protein HP0245(EC) formulated in aluminum hydroxide adjuvant provided 100% protection in mice challenged with a low dose (2 × LD(50) ) of SS2. However, 80% and 50% survival rates were observed in mice vaccinated with HP0245(EC) and SS2 bacterin, respectively, challenged with a high dose (5 × LD(50) ) of SS2. Immunization with HP0245(EC) induced significantly higher IgG2a titers compared with SS2 bacterin, which was more effective for opsonophagocytosis. No obvious histopathological change was found in the HP0245(EC) -vaccinated mice after challenge with the low dose of SS2, whereas a mild lesion was observed in the meninges of the mice vaccinated with SS2 bacterin. Homologous hp0245 genes with the highly conserved coding sequence of the extracellular peptide exist in all sequenced SS2 strains as well as most S. suis reference strains. Thus, HP0245 could be considered as a promising vaccine candidate for SS2.

Comparative Proteomic Analyses of Streptococcus suis Serotype 2 Cell Wall-Associated Proteins

Streptococcus suis serotype 2 (SS2) is a zoonotic pathogen that is distributed throughout the world. Virulence factors and/or markers of the virulent serotype 2 strains have not been fully identified. In this study a simple, rapid, and non-destructive method was used to extract cell wall-associated proteins from SS2 strains. Two virulent strains were compared with one avirulent strain by 2-dimensional electrophoresis (2DE). When the results of the 2DE analyses were combined with the results of mass spectrometry analyses, a total of 40 unique proteins were identified, including 26 antigens (2DE immunoblotting was used as a preliminary study). In addition to a known virulence factor, muramidase-released protein, two new proteins, catabolite control protein A and leucyl aminopeptidase, and nine potential virulence factors were also identified. The formers may be a potential virulence regulator or drug target, and the latter contains plasminogen-binding proteins and molecular chaperones. Our results complemented previous immunoproteomics studies of SS2 strains.

A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates

Background Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood.Methods and FindingsTo elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ∼89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence.ConclusionsTo our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.