Explore the vast range of titles available.

Streptococcus suis is a systemic pathogen of swine and imposes a significant economic burden on the swine industry. Disease with S. suis is controlled with antibiotic treatment and vaccination with inactivated vaccines, which can be derived from the strains circulating on the farm. Inactivated vaccines have shown mixed results with minimal data supporting reductions in morbidity and mortality following their use. With increasing restrictions on antibiotic use and increasing concerns surrounding antimicrobial resistance, alternatives to antibiotics or novel, highly effective vaccines are needed for treating or preventing disease with S. suis . Bacteriocins are a potential alternative to antibiotics, as bacteriocins are antimicrobial peptides produced by bacteria. However, the use of bacteriocins to limit pathogenic S. suis remains relatively under-examined. Live vaccines are a potential novel and effective method of preventing disease, as they provide competition for pathogenic strains and would limit pathogenic strain colonization while stimulating a protective immune response. This study investigated the use of an avirulent, bacteriocin producing isolate of S. suis (90–1330) as an intranasal vaccine and evaluated the role of the bacteriocin by comparing protection to animals inoculated with a mutant lacking bacteriocin production (90–1330Δ suicin ). Animals were protected from systemic disease when challenged with a virulent isolate 21 days after inoculation with either 90–1330 or 90–1330Δ suicin but were not protected when challenged 3 days after inoculation. Evaluation of antibody titers showed increased titers 21 days post-inoculation, and the humoral response was likely providing systemic protection. Although 90–1330 was unable to protect animals challenged 3 days post-inoculation, the strain should be considered a good candidate for vaccine development. S. suis 90–1330 was able to induce a protective immune response with a single intranasal inoculation and bacteriocin production may be able to contribute to protection when animals have a lower exposure dose, as in a production setting.

Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the contribution of the inflammatory response to STSLS, the precise mechanism underlying STSLS development remains elusive. Here, we use a murine model to demonstrate that caspase-1 activity is critical for STSLS development. Furthermore, we show that inflammasome activation by S. suis is mainly dependent on NLRP3 but not on NLRP1, AIM2 or NLRC4. The important role of NLRP3 activation in STSLS is further confirmed in vivo with the NLRP3 inhibitor MCC950 and nlrp3-knockout mice. By comparison of WT strain with isogenic strains with mutation of various virulence genes for inflammasome activation, Suilysin is essential for inflammasome activation, which is dependent on the membrane perforation activity to cause cytosolic K+ efflux. Moreover, the mutant strain msly (P353L) expressing mutagenic SLY without hemolytic activity was unable to activate the inflammasome and does not cause STSLS. In summary, we demonstrate that the high membrane perforation activity of the epidemic strain induces a high level of NLRP3 inflammasome activation, which is essential for the development of the cytokine storm and multi-organ dysfunction in STSLS and suggests NLRP3 inflammasome as an attractive target for the treatment of STSLS.

Background Streptococcus suis is divided into 29 serotypes based on a serological reaction against the capsular polysaccharide (CPS). Multiplex PCR tests targeting the cps locus are also used to determine S. suis serotypes, but they cannot differentiate between serotypes 1 and 14, and between serotypes 2 and 1/2. Here, we developed a pipeline permitting in silico serotype determination from whole-genome sequencing (WGS) short-read data that can readily identify all 29  S. suis serotypes. Results We sequenced the genomes of 121 strains representing all 29 known S. suis serotypes. We next combined available software into an automated pipeline permitting in silico serotyping of strains by differential alignment of short-read sequencing data to a custom S. suis cps loci database. Strains of serotype pairs 1 and 14, and 2 and 1/2 could be differentiated by a missense mutation in the cpsK gene . We report a 99 % match between coagglutination- and pipeline-determined serotypes for strains in our collection. We used 375 additional S. suis genomes downloaded from the NCBI’s Sequence Read Archive (SRA) to validate the pipeline. Validation with SRA WGS data resulted in a 92 % match. Included pipeline subroutines permitted us to assess strain virulence marker content and obtain multilocus sequence typing directly from WGS data. Conclusions Our pipeline permits rapid and accurate determination of S. suis serotype, and other lineage information, directly from WGS data. By discriminating between serotypes 1 and 14, and between serotypes 2 and 1/2, our approach solves a three-decade longstanding S. suis typing issue.

Streptococcus suis is a major swine pathogen responsible for important economic losses to the swine industry worldwide. It is also an emerging zoonotic agent of meningitis and streptococcal toxic shock-like syndrome. Since the recent recognition of the high prevalence of S. suis human disease in southeast and east Asia, the interest of the scientific community in this pathogen has significantly increased. In the last few years, as a direct consequence of these intensified research efforts, large amounts of data on putative virulence factors have appeared in the literature. Although the presence of some proposed virulence factors does not necessarily define a S. suis strain as being virulent, several cell-associated or secreted factors are clearly important for the pathogenesis of the S. suis infection. In order to cause disease, S. suis must colonize the host, breach epithelial barriers, reach and survive in the bloodstream, invade different organs, and cause exaggerated inflammation. In this review, we discuss the potential contribution of different described S. suis virulence factors at each step of the pathogenesis of the infection. Finally, we briefly discuss other described virulence factors, virulence factor candidates and virulence markers for which a precise role at specific steps of the pathogenesis of the S. suis infection has not yet been clearly established.

Streptococcus suis (S. suis) is a major pathogen that poses a long-term threat to swine populations. Due to its foodborne transmission, this pathogen has recently emerged as a leading cause of meningitis in humans, presenting a significant public health challenge. Currently, no vaccine is available to combat this disease, particularly a universal vaccine capable of addressing multiple subtypes of S. suis. In this study, we developed a universal live vaccine candidate against multiple serotypes S. suis based on the polyvalent antigen protein SE6. A live Salmonella Choleraesuis (S. Choleraesuis) vector was employed for the production and in vivo delivery of the polyvalent antigen. The SE6 protein was efficiently expressed within the S. Choleraesuis vector and delivered to the host's lymphatic system. The antiserum of mice immunized with SE6-delivering S. Choleraesuis vector produced a broader and potent opsonophagocytic response against multiple serotypes of S. suis. Finally, the SE6-delivering S. Choleraesuis vector demonstrated high efficacy in providing protection against S. suis serotypes 2, 7, and 9 in vivo. •A live Salmonella Choleraesuis vector rSC0016 that carries a SE6 polyvalent antigen.•The SE6 protein was efficiently expressed within the S. choleraesuis vector rSC0016.•rSC0016(pS-SE6) induces good mucosal, humoral, and cellular immune responses.•rSC0016(pS-SE6) protects against Streptococcus suis serotypes 2, 7, and 9 in mice.

Streptococcussuis is an important zoonotic agent causing severe diseases in pigs and humans. To date, 33 serotypes of S. suis have been identified based on antigenic differences in the capsular polysaccharide. The capsular polysaccharide synthesis (cps) locus encodes proteins/enzymes that are responsible for capsular production and variation in the capsule structures are the basis of S. suis serotyping. Multiplex and/or simplex PCR assays have been developed for 15 serotypes based on serotype-specific genes in the cps gene cluster. In this study, we developed a set of multiplex PCR (mPCR) assays to identify the 33 currently known S. suis serotypes. To identify serotype-specific genes for mPCR, the entire genomes of reference strains for the 33 serotypes were sequenced using whole genome high-throughput sequencing, and the cps gene clusters from these strains were identified and compared. We developed a set of 4 mPCR assays based on the polysaccharide polymerase gene wzy, one of the serotype-specific genes. The assays can identify all serotypes except for two pairs of serotypes: 1 and 14, and 2 and 1/2, which have no serotype-specific genes between them. The first assay identifies 12 serotypes (serotypes 1 to 10, 1/2, and 14) that are the most frequently isolated from diseased pigs and patients; the second identifies 10 serotypes (serotypes 11 to 21 except 14); the third identifies the remaining 11 serotypes (serotypes 22 to 31, and 33); and the fourth identifies a new cps cluster of S. suis discovered in this study in 16 isolates that agglutinated with antisera for serotypes 29 and 21. The multiplex PCR assays developed in this study provide a rapid and specific method for molecular serotyping of S. suis.

Streptococcus suis is a severe zoonotic pathogen affecting weaned piglets. No commercial vaccine that provides protection against S. suis is available. A prototype vaccine, tentatively called VASIP (Vaccine Against Streptococcus suis Infection in Pigs), composed of five recombinant fusion proteins, encompassing 23 different protein domains, was used in this study. Pregnant sows were vaccinated on three occasions, at 68, 47 and 19 days prior to farrowing, resulting in high antibody levels, both in sera and in colostrum. Antibodies were transferred to the litter via colostrum. The litters from VASIP-vaccinated and placebo-vaccinated sows were challenged intravenously with S. suis at four or seven weeks of age in two different arms of the study. Body temperature and clinical signs (demeanour, behavioural CNS, and mobility) of infection showed that piglets from vaccinated sows were significantly protected against S. suis infection in the 4-week-old group and that the incidence of severe clinical signs was lower in the 7-week-old group compared with piglets from placebo sows. The study demonstrates the feasibility of vaccinating sows, rather than piglets, using recombinant fusion proteins to maximise protection against S. suis during the period in which they are most at risk of disease. •An efficacious vaccine against Streptococcus suis has been constructed.•The vaccine encompasses 23 protein fragments in five fusion proteins.•The purification processes of the fusion proteins allow large scale manufacturing.•Vaccinating pregnant sows confers protection to the litter via colostrum.•Piglets from vaccinated sows were protected against a high-dose intravenous challenge with S. suis.

Streptococcus suis is an important meningitis‐causing pathogen in pigs and humans. Neutrophil extracellular traps (NETs) have been identified as host defense mechanism against different pathogens. Here, NETs were detected in the cerebrospinal fluid (CSF) of S. suis‐infected piglets despite the presence of active nucleases. To study NET‐formation and NET‐degradation after transmigration of S. suis and neutrophils through the choroid plexus epithelial cell barrier, a previously described model of the human blood‐CSF barrier was used. NETs and respective entrapment of streptococci were recorded in the “CSF compartment” despite the presence of active nucleases. Comparative analysis of S. suis wildtype and different S. suis nuclease mutants did not reveal significant differences in NET‐formation or bacterial survival. Interestingly, transcript expression of the human cathelicidin LL‐37, a NET‐stabilizing factor, increased after transmigration of neutrophils through the choroid plexus epithelial cell barrier. In good accordance, the porcine cathelicidin PR‐39 was significantly increased in CSF of piglets with meningitis. Furthermore, we confirmed that PR‐39 is associated with NETs in infected CSF and inhibits neutrophil DNA degradation by bacterial nucleases. In conclusion, neutrophils form NETs after breaching the infected choroid plexus epithelium, and those NETs may be protected by antimicrobial peptides against bacterial nucleases.

Streptococcus suis, more particularly serotype 2, is a major swine pathogen and an emerging zoonotic agent worldwide that mainly causes meningitis, septicemia, endocarditis, and pneumonia. Although several potential virulence factors produced by S. suis have been identified in the last decade, the pathogenesis of S. suis infections is still not fully understood. In the present study, we showed that S. suis produces membrane vesicles (MVs) that range in diameter from 13 to 130 nm and that appear to be coated by capsular material. A proteomic analysis of the MVs revealed that they contain 46 proteins, 9 of which are considered as proven or suspected virulence factors. Biological assays confirmed that S. suis MVs possess active subtilisin-like protease (SspA) and DNase (SsnA). S. suis MVs degraded neutrophil extracellular traps, a property that may contribute to the ability of the bacterium to escape the host defense response. MVs also activated the nuclear factor-kappa B (NF-κB) signaling pathway in both monocytes and macrophages, inducing the secretion of pro-inflammatory cytokines, which may in turn contribute to increase the permeability of the blood brain barrier. The present study brought evidence that S. suis MVs may play a role as a virulence factor in the pathogenesis of S. suis infections, and given their composition be an excellent candidate for vaccine development.

Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis -associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.