Streptococcus suis

1. Overview

Streptococcus suis is a Gram-positive, facultatively anaerobic coccus of the family Streptococcaceae and genus Streptococcus, and is a major zoonotic pathogen affecting both pigs and humans. The bacterium causes substantial economic losses in the global pork industry and can cause meningitis, septicemia, endocarditis, and the frequently fatal streptococcal toxic shock-like syndrome (STSLS) in humans.

Based on capsular polysaccharide (CPS) antigenicity, 29 serotypes have been identified, among which serotype 2 (SS2) is the most frequently isolated from diseased pigs and the predominant cause of human infections. The case-fatality rate for SS2 infection exceeds 20%, and survivors often suffer from permanent neurological sequelae including hearing loss and cognitive impairment. Large-scale outbreaks in China during 1998 and 2005 resulted in over 200 human cases, establishing SS2 as an emerging zoonotic threat. Sporadic cases continue to occur across Southeast Asia, with increasing reports from Europe and South America, reflecting the global expansion of this pathogen. The asymptomatic carriage rate in pig herds is approximately 60%–100%.

2. Background Information

2.1 What is Streptococcus suis?

S. suis is a Gram-positive facultatively anaerobic coccus of the family Streptococcaceae. The bacterium is commonly found as part of the commensal microbiota in the upper respiratory tract of swine but can transition to a pathogen under certain conditions, causing bacteremia, endocarditis, arthritis, pneumonia, and meningitis. In Europe, approximately 80% of pig production units are clinically affected by S. suis infections. In Vietnam, Thailand, and China, S. suis is one of the leading causes of bacterial meningitis, while incidence rates in Europe range from 0.1 to 4.9 cases per 100,000 individuals.

2.2 Genome & Classification

The S. suis genome is a circular chromosome of approximately 2.0–2.1 Mb. Through multilocus sequence typing (MLST), over 4,200 sequence types (STs) have been identified to date, reflecting the extremely high genetic variability of this bacterium, which complicates the development of broadly protective vaccines. S. suis produces over 70 virulence factors, several of which have been extensively studied as potential vaccine targets.

2.3 What Are S. suis Virulence Factors？

The virulence factors of S. suis primarily include:

2.3.1 Dynamic Regulation of Capsular Polysaccharide (CPS)

A 2025 study published in eLife revealed the dynamic regulation of CPS during S. suis pathogenesis. Using an intranasal infection model (simulating the natural route of infection), the study found:

l Thin or no CPS was associated with efficient binding of SS2 strain 05ZYH33 to respiratory epithelial cells

l Thick CPS increased resistance to blood clearance

l 05ZYH33 was detected in nasal-associated lymphoid tissue (NALT) and cerebrospinal fluid (CSF) as early as 30 minutes after intranasal inoculation without bacteremia

l Histological analysis revealed that 05ZYH33 in the nasal cavity invaded the olfactory epithelium, resulting in early brain inflammation

l Transmission electron microscopy showed that bacteria isolated from NALT and CSF at early infection had a thin layer of CPS, while those detected in the blood 5 hours post-inoculation showed a much thicker CPS

l Anti-CPS antiserum restricted 05ZYH33 in the blood but not in NALT or CSF

l Antiserum directed to multiple non-CPS virulence factors (anti-V5) efficiently inhibited 05ZYH33 in NALT, CSF, and blood

These findings indicate that SS2 colonizes NALT efficiently without CPS and subsequently invades the meninges through the olfactory nerve system, while CPS upregulation aids survival in the bloodstream. This provides new directions for cross-serotype vaccine development by targeting CPS-independent immunity.

2.3.2 Ihk/Irr-PepO Axis

A 2025 study published in Veterinary Microbiology identified a two-component system named Ihk/Irr as a key regulator of SS2 resistance to macrophage phagocytosis. Phosphorylation of histidine at position 246 (H246) in Ihk and aspartate at position 52 (D52) in Irr enhances SS2 anti-phagocytic capacity and virulence. Irr directly binds to the pepO promoter, while the phosphorylation-site inactivation protein Irr-D52A loses this binding ability. SS2 regulates PepO expression by sensing extracellular stimuli through Ihk/Irr phosphorylation; PepO subsequently activates the p38 and ERK1/2 pathways via TLR2, leading to enhanced phosphorylation that ultimately inhibits actin polymerization, impairing phagocytosis and thereby enhancing SS2's phagocytosis resistance.

2.3.3 ShgH Dual Transporter

A 2025 study published in ScienceDirect characterized ShgH, a predicted substrate-binding component of an ABC transporter. Isothermal titration calorimetry demonstrated that ShgH binds glutamine and histidine, with a higher affinity for histidine. Deletion of the shgH gene significantly impaired uptake of radiolabelled amino acids, confirming its role as part of a transporter. Functional analysis revealed that shgH deletion results in a marked reduction in virulence in a murine infection model, while host colonization remained unaffected. ShgH contributes to infection by facilitating evasion of phagocytosis and resistance to oxidative stress through impaired nutrient acquisition and reduced capsule production, and regulates biofilm formation and architecture.

2.4 Mechanism of Infection and Pathogenesis

2.4.1 Colonization and Invasion

S. suis infection begins with bacterial colonization of the porcine upper respiratory tract. A 2025 eLife study revealed that SS2 can reach the meninges via the olfactory route before bacteremia occurs. The specific process is:

a. Thin-CPS SS2 efficiently binds respiratory epithelial cells

b. Bacteria colonize NALT early

c. Bacteria invade through the olfactory epithelium and travel along the olfactory nerve to the meninges

d. In the blood, bacteria upregulate CPS expression to resist blood clearance

2.4.2 Immune Evasion Mechanisms

S. suis evades host immune clearance through multiple mechanisms:

l Anti-phagocytosis: The Ihk/Irr-PepO axis resists phagocytosis by inhibiting macrophage actin polymerization

l CPS-mediated immune masking: Thick CPS masks surface immunogenic components, inhibiting complement deposition and phagocytosis

l Nutrient acquisition systems: Transporters such as ShgH ensure nutrient supply in the host environment, supporting survival under oxidative stress

2.4.3 Blood-Brain Barrier Disruption and Excessive Inflammation

Suilysin is a key virulence factor that disrupts the blood-brain barrier by directly damaging endothelial cells through pore formation, promoting bacterial invasion of the central nervous system. Massive bacterial proliferation and toxin release trigger excessive inflammation, ultimately leading to STSLS, characterized by high fever, shock, and multi-organ failure.

2.4.4 Regulatory Networks

S. suis virulence is controlled by a complex regulatory network including two-component systems, Ser/Thr kinase STK, small RNAs, toxin-antitoxin modules, and the stringent response. STK enhances SS2 acid resistance by phosphorylating the substrate FadR at Thr230, thereby improving survival in the gastric acid environment.

2.5 Transmission Routes and Process

Transmission of S. suis occurs primarily through the following routes:

l Direct contact transmission: Through broken skin or mucous membranes contacting infected pigs or their body fluids; the primary route for occupational groups (pig farm workers, abattoir workers, veterinarians)

l Foodborne transmission: Consumption of raw or undercooked pork products; an important route of human infection in Southeast Asia and Asia

l Environmental exposure: In the 2025 Henan case of S. parasuis, the patient was a sanitation worker with no documented livestock contact, suggesting environmental exposure as a possible transmission route

Process: Bacterial colonization of the upper respiratory tract → entry through broken skin/mucosa or ingestion → thin-CPS form colonizes NALT → olfactory route or hematogenous dissemination to the meninges → blood-brain barrier disruption → meningitis/septicemia/STSLS.

2.6 Symptoms and Treatment

2.6.1 Clinical Symptoms

Clinical manifestations of human S. suis infection include:

l Meningitis: Most common presentation; headache, fever, neck stiffness

l Septicemia: High fever, chills, systemic inflammatory response

l STSLS: Case-fatality rate exceeds 20%; presents with shock and multi-organ failure

l Endocarditis: Can lead to valve damage

l Permanent sequelae: Survivors often experience hearing loss and cognitive impairment

2.6.2 Treatment

First-line antimicrobials: β-lactams (penicillin G, ampicillin, ceftriaxone) and fluoroquinolones.

Resistance challenges: S. suis exhibits resistance to a diverse array of antibiotics, including macrolides, lincosamides, aminoglycosides, chloramphenicol, β-lactams, fluoroquinolones, and tetracyclines. Multidrug-resistant strains have emerged in China, posing substantial challenges for therapeutic strategies.

Novel therapeutic strategies:

l Targeting LDH to reverse aminoglycoside resistance: A 2025 study found that panaxadiol (PD) and vitamin D2 (VD2) inhibit S. suis lactic dehydrogenase, redirecting metabolism from lactic acid fermentation to the tricarboxylic acid cycle, increasing NADH production and proton motive force (PMF), thereby enhancing aminoglycoside uptake and bactericidal activity

l Antimicrobial peptide-antibiotic synergy: CATH-1 combined with tetracycline rapidly killed all tested bacteria within 60 minutes, with mechanisms involving membrane disruption, ROS induction, and biofilm inhibition

2.7 Prevention

l Herd management: Strengthen biosecurity measures on pig farms, implement all-in/all-out systems to reduce S. suis transmission within pig populations

l Food safety: Thoroughly cook pork products; avoid raw or undercooked pork; separate raw and cooked foods to prevent cross-contamination

l Occupational protection: Pig farm workers, abattoir workers, and veterinarians should wear appropriate personal protective equipment (gloves, protective clothing, masks) when handling pigs

l Hand hygiene: Thoroughly wash hands after contact with pigs or raw pork

l Wound care: Promptly clean and cover broken skin to avoid contact with infectious sources

l Surveillance and reporting: Strengthen human S. suis infection surveillance, particularly in pig-dense areas and occupationally exposed populations

2.8 Targets for Intervention

2.8.1 Pathogen Targets

2.8.2 Host Targets

2.9 Vaccine Types and Development Progress

Currently, no effective commercial S. suis vaccine is available globally. Current strategies are limited by the high genetic and antigenic diversity of the bacterium.

2.9.1 Capsular Polysaccharide Conjugate Vaccine

A 2025 study published in Vaccine developed a CPS2-protein conjugate vaccine. The study established a novel, reliable CPS2 purification method combining polyethylenimine-mediated nucleic acid precipitation with phenol-based protein denaturation, eliminating the need for column chromatography and enabling gram-scale CPS2 recovery per liter of culture. By comparing native and desialylated CPS2 conjugates, the study found that sialic acid is important for immune recognition but has limited impact on vaccine efficacy. The native CPS2 conjugate vaccine induced robust IgG responses in pigs and conferred significant protection against virulent SS2 challenge.

2.9.2 Manganese Transporter Mutant Live Attenuated Vaccine

A 2025 study published in Veterinary Microbiology constructed a live attenuated vaccine lacking the major manganese transporter. Evaluation in pigs showed that the vaccine was safe and efficacious at 10¹⁰ CFU, but a 10⁹ CFU lower dose failed to generate significant immune protection. Notably, four pigs receiving the adjuvanted vaccine died during the vaccination phase; analysis suggested that the vaccine strain reverted to virulence—the vaccine strain acquired compensatory mutations that upregulated a secondary manganese transporter, restoring virulence.

2.9.3 Epitope-Based Multimeric Subunit Vaccine (ATOMSSUISpenta)

A 2025 study published in Europe PMC developed ATOMSSUISpenta, an epitope-based multimeric subunit vaccine. The vaccine conferred significant protection against S. suis serotypes 2, 4, and 9, demonstrated by improved survival rates and reduced bacterial burdens, highlighting the broad-spectrum protective potential of epitope-based multimeric design for targeting antigenically diverse Gram-positive pathogens.

2.9.4 Universal Live Vaccine Platform Based on Polyvalent Antigen Protein

A 2025 study published in Vaccine developed a universal live vaccine platform based on the polyvalent antigen protein SE6. Using Salmonella Choleraesuis as the delivery vector, the SE6-delivering S. Choleraesuis vector demonstrated high efficacy in providing protection against S. suis serotypes 2, 7, and 9 in vivo.

2.9.5 Oral Subunit Vaccine Delivery Technology

In 2025, the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences successfully developed a novel oral subunit vaccine delivery technology. The research team used genetic engineering to reduce the endotoxin activity of an attenuated Salmonella Choleraesuis strain, prepared biomimetic vesicles, and introduced a dual-antigen coupling system with chitosan oligosaccharide coating to achieve oral delivery of S. suis serotype 2 and pseudorabies virus subunit vaccines.

2.10 Drugs

2.10.1 Pathogen-Targeted Drugs

2.10.2 Antimicrobial Agents

2.11 Recent Research

2.11.1 Molecular Epidemiology and Resistance Surveillance

A 2025 study published in Springer investigated 315 S. suis isolates collected from clinically healthy pigs in Guangdong and Guangxi, China, between 2024 and 2025, finding that multidrug-resistant and virulent strains are widespread in clinically healthy pigs, posing an increasingly serious threat to human health. In Nakhon Ratchasima, Thailand, 93 human S. suis cases with 13 deaths were reported in 2025, the highest number reported in Thailand to date. Hue Central Hospital in Vietnam recorded 31 human infection cases in 2025.

2.11.2 Emergence of a Novel Human Pathogen — Streptococcus parasuis

In 2025, Henan Province, China reported the first human case of Streptococcus parasuis infection. The patient was a 69-year-old male sanitation worker whose left foot was crushed by a garbage truck, with no documented livestock contact. MALDI-TOF MS initially identified the isolate as S. suis, but S. suis-specific qPCR produced a negative result; average nucleotide identity (ANI) analysis definitively identified it as S. parasuis, distantly related to previously reported clinical isolates from China. This case suggests that environmental exposure may be a transmission route and recommends including S. parasuis in the differential diagnosis for severe traumatic infections even in the absence of livestock contact history.

2.11.3 Diagnostic Technology Advances

Isothermal amplification: In 2025 technological advances, loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA) have been applied for rapid detection of S. suis, suitable for field applications in resource-limited settings.

CRISPR-Cas detection: CRISPR-Cas-based nucleic acid detection methods for S. suis are under development, offering high sensitivity and specificity.

MALDI-TOF MS combined with qPCR: In the 2025 Henan case, MALDI-TOF MS preliminary identification combined with species-specific qPCR successfully distinguished S. suis from S. parasuis, demonstrating the importance of molecular diagnostics for species-level identification.

2.11.4 Trained Immunity Strategies

Studies published in 2025–2026 explored trained immunity as a potential strategy to complement vaccination. Pigs immunized with a mycobacterial-derived immunomodulator (dpB) combined with a specific S. suis vaccine showed better responses in the vaccine + inactivated dpB group, including reduced bacterial loads in tissues, less severe lung lesions, and elevated pre-challenge cytokine levels.

3. Related Products & Services

l Recombinant Antigens & Receptors

l Antibodies

l Detection Kits

l Recombinant Protein Expression Services

l Antibody Development Services

4. Resources

5. References

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2. Yang, K., Wang, Q., Liu, M., et al. (2025). Streptococcus suis employs the Ihk/Irr-PepO axis to subvert macrophage actin polymerization: A novel anti-phagocytic strategy enhancing bacterial virulence. Veterinary microbiology, 310, 110726.

3. García, C., Saralegui, L., Morales, B., et al. (2026). Identification of ShgH as a dual histidine/glutamine transporter component essential for Streptococcus suis virulence and biofilm modulation. Microbiological research, 302, 128354.

4. Zhao, G., Ying, L., Shi, Y., et al. (2024). Potential mechanisms of Streptococcus suis virulence-related factors in blood-brain barrier disruption. One Health Advances, 2, 26.

5. Sui, Y., Chen, Y., Lv, Q., et al. (2022). Suilyin Disrupts the Blood-Brain Barrier by Activating Group III Secretory Phospholipase A2. Life (Basel, Switzerland), 12(6), 919.

6. Wiebe, M., Ingebritson, A., Sholeh, M., et al. (2025). Streptococcus suis manganese transporter mutant as a live attenuated vaccine: Safety, efficacy, and virulence reversion mechanisms. Veterinary microbiology, 305, 110521.

7. Zhong, Y., Yang, H., Chai, W., et al. (2026). Development and immunological evaluation of a Streptococcus suis serotype 2 capsular polysaccharide conjugate vaccine. Vaccine, 69, 128004.

8. Kim, S. Y., Chen, F., Kim, W. S., et al. (2026). Epitope-Based Multimeric Subunit Vaccine (ATOMSSUISpenta) Confers Broad Protection Against Streptococcus suis Infection. The Journal of infectious diseases, 233(5), 899–911.

9. Li, W., Li, Y. A., Wang, S., et al. (2025). A universal live vaccine platform against multiple serotypes Streptococcus suis based on polyvalent antigen protein. Vaccine, 47, 126700.

10. Sánchez-Morales, L., Pérez-Sancho, M., García-Seco, T., et al. (2025). Exploring trained immunity to complement vaccination against Streptococcus suis in swine. Developmental and comparative immunology, 172, 105498.

11. Pan, Y., Liu, H., Liu, Y., et al. (2025). Antimicrobial peptide-antibiotic synergy exerts anti-streptococcus suis infection by membrane disruption, ROS induction and biofilm inhibition. International immunopharmacology, 161, 115053.

12. Gao, S., Quan, Y., Song, S., et al. (2025). Disrupting bacterial metabolism by targeting LDH reverses aminoglycoside resistance in Streptococcus suis. International journal of antimicrobial agents, 66(6), 107599.

13. Uruén, C., Fernandez, A., Arnal, J. L., et al. (2024). Genomic and phenotypic analysis of invasive Streptococcus suis isolated in Spain reveals genetic diversification and associated virulence traits. Veterinary research, 55(1), 11.

14. Hatrongjit, R., Fittipaldi, N., Gottschalk, M., et al. (2024). Genomic epidemiology in Streptococcus suis: Moving beyond traditional typing techniques. Heliyon, 10(6), e27818.

15. Tram, G., Jennings, M. P., Blackall, P. J., et al. (2021). Streptococcus suis pathogenesis-A diverse array of virulence factors for a zoonotic lifestyle. Advances in microbial physiology, 78, 217–257.