ABSTRACT
Streptococcus suis serotype 2 is an important encapsulated bacterial swine pathogen and zoonotic agent for which no effective vaccine exists. The interaction with B cells and the humoral response against S. suis are poorly understood despite their likely relevance for a potential vaccine. We evaluated germinal center (GC) B cell kinetics, as well as the production and role of S. suis-specific antibodies following infections in a mouse model. We found that mice infected with S. suis developed GC that peaked 13-21 days post-infection. GC further increased and persisted upon periodic reinfection that mimics real life conditions in swine farms. Anti-S. suis IgM and several IgG subclasses were produced, but antibodies against the S. suis capsular polysaccharide (CPS) were largely IgM. Interestingly, depletion of total IgG from the wild-type mice sera had no effect on bacterial killing by opsonophagocytosis in vitro. Somatic hypermutation and isotype switching were dispensable for controlling the infection or anti-CPS IgM production. However, T cell-deficient (Tcrb-/-) mice were unable to control bacteremia, produce optimal anti-CPS IgM titers, or elicit antibodies with opsonophagocytic activity. SAP deficiency, which prevents GC formation but not extrafollicular B cell responses, ablated anti S. suis-IgG production but maintained IgM production and eliminated the infection. In contrast, B cell deficient mice were unable to control bacteremia. Collectively, our results indicate that the antibody response plays a large role in immunity against S. suis, with GC-independent but T cell-dependent germline IgM being the major effective antibody specificities. Our results further highlight the importance IgM, and potentially anti-CPS antibodies, in clearing S. suis infections and provide insight for future development of S. suis vaccines.
Subject(s)
Bacteremia , Streptococcal Infections , Streptococcus suis , Vaccines , Animals , Mice , Swine , Streptococcus suis/genetics , Antibodies, Bacterial , Immunoglobulin G , Immunoglobulin M , T-Lymphocytes , Streptococcal Infections/microbiologyABSTRACT
Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite their importance, the mechanism underlying the stable inheritance of ICEs, which is necessary for the acquisition of new traits in bacteria, remains poorly understood. Here, we identified SezAT, a type II toxin-antitoxin (TA) system, and AbiE, a type IV TA system encoded within the ICESsuHN105, coordinately promote ICE stabilization and mediate multidrug resistance in Streptococcus suis. Deletion of SezAT or AbiE did not affect the strain's antibiotic susceptibility, but their duple deletion increased susceptibility, mainly mediated by the antitoxins SezA and AbiEi. Further studies have revealed that SezA and AbiEi affect the genetic stability of ICESsuHN105 by moderating the excision and extrachromosomal copy number, consequently affecting the antibiotic resistance conferred by ICE. The DNA-binding proteins AbiEi and SezA, which bind palindromic sequences in the promoter, coordinately modulate ICE excision and extracellular copy number by binding to sequences in the origin-of-transfer (oriT) and the attL sites, respectively. Furthermore, AbiEi negatively regulates the transcription of SezAT by binding directly to its promoter, optimizing the coordinate network of SezAT and AbiE in maintaining ICESsuHN105 stability. Importantly, SezAT and AbiE are widespread and conserved in ICEs harbouring diverse drug-resistance genes, and their coordinated effects in promoting ICE stability and mediating drug resistance may be broadly applicable to other ICEs. Altogether, our study uncovers the TA system's role in maintaining the genetic stability of ICE and offers potential targets for overcoming the dissemination and evolution of drug resistance.
Subject(s)
Bacterial Proteins , Streptococcus suis , Toxin-Antitoxin Systems , Streptococcus suis/genetics , Streptococcus suis/drug effects , Toxin-Antitoxin Systems/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Streptococcal Infections/microbiology , Streptococcal Infections/genetics , Anti-Bacterial Agents/pharmacology , Conjugation, Genetic , Animals , Interspersed Repetitive SequencesABSTRACT
BACKGROUND: Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear. RESULTS: Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis. CONCLUSIONS: Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces' RPSA.
Subject(s)
Streptococcal Infections , Streptococcus suis , Humans , Animals , Swine , Endothelial Cells/metabolism , Serogroup , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Brain/metabolism , Apoptosis , Ribosomal Proteins/metabolism , Streptococcal Infections/metabolism , Streptococcal Infections/microbiologyABSTRACT
The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.
Subject(s)
Cytokines , Endosomes , Interferon Type I , Signal Transduction , Streptococcus suis , Toll-Like Receptor 2 , Streptococcus suis/immunology , Streptococcus suis/pathogenicity , Streptococcus suis/metabolism , Interferon Type I/metabolism , Toll-Like Receptor 2/metabolism , Cytokines/metabolism , Animals , Endosomes/metabolism , Mice , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Streptococcal Infections/metabolism , Bacterial Proteins/metabolism , Type IV Secretion Systems/metabolism , Type IV Secretion Systems/genetics , Humans , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/genetics , Mice, Inbred C57BLABSTRACT
In Jeju Island, South Korea, a patient who consumed raw pig products had subdural empyema, which led to meningitis, sepsis, and status epilepticus. We identified Streptococcus suis from blood and the subdural empyema. This case illustrates the importance of considering dietary habits in similar clinical assessments to prevent misdiagnosis.
Subject(s)
Empyema, Subdural , Sepsis , Streptococcal Infections , Streptococcus suis , Humans , Animals , Swine , Empyema, Subdural/diagnosis , Streptococcus suis/genetics , Republic of Korea , Feeding Behavior , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapyABSTRACT
Streptococcus suis, a zoonotic bacterial pathogen circulated through swine, can cause severe infections in humans. Because human S. suis infections are not notifiable in most countries, incidence is underestimated. We aimed to increase insight into the molecular epidemiology of human S. suis infections in Europe. To procure data, we surveyed 7 reference laboratories and performed a systematic review of the scientific literature. We identified 236 cases of human S. suis infection from those sources and an additional 87 by scanning gray literature. We performed whole-genome sequencing to type 46 zoonotic S. suis isolates and combined them with 28 publicly available genomes in a core-genome phylogeny. Clonal complex (CC) 1 isolates accounted for 87% of typed human infections; CC20, CC25, CC87, and CC94 also caused infections. Emergence of diverse zoonotic clades and notable severity of illness in humans support classifying S. suis infection as a notifiable condition.
Subject(s)
Molecular Epidemiology , Phylogeny , Streptococcal Infections , Streptococcus suis , Zoonoses , Streptococcus suis/genetics , Streptococcus suis/classification , Streptococcal Infections/epidemiology , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Europe/epidemiology , Humans , Animals , Zoonoses/epidemiology , Swine , Whole Genome Sequencing , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/microbiology , Bacterial Zoonoses/epidemiology , Bacterial Zoonoses/microbiology , Swine Diseases/epidemiology , Swine Diseases/microbiologyABSTRACT
BACKGROUND: Streptococcus suis is an important pig pathogen and an emerging zoonotic agent. In a previous study, we described a high proportion of penicillin-resistant serotype 9 S. suis (SS9) isolates on pig farms in Italy. OBJECTIVES: We hypothesized that resistance to penicillin emerged in some SS9 lineages characterized by substitutions at the PBPs, contributing to the successful spread of these lineages in the last 20 years. METHODS: Sixty-six SS9 isolates from cases of streptococcosis in pigs were investigated for susceptibility to penicillin, ceftiofur and ampicillin. The isolates were characterized for ST, virulence profile, and antimicrobial resistance genes through WGS. Multiple linear regression models were employed to investigate the associations between STs, year of isolation, substitutions at the PBPs and an increase in MIC values to ß-lactams. RESULTS: MIC values to penicillin increased by 4% each year in the study period. Higher MIC values for penicillin were also positively associated with ST123, ST1540 and ST1953 compared with ST16. The PBP sequences presented a mosaic organization of blocks. Within the same ST, substitutions at the PBPs were generally more frequent in recent isolates. Resistance to penicillin was driven by substitutions at PBP2b, including K479T, D512E and K513E, and PBP2x, including T551S, while reduced susceptibility to ceftiofur and ampicillin were largely dependent on substitutions at PBP2x. CONCLUSIONS: Here, we identify the STs and substitutions at the PBPs responsible for increased resistance of SS9 to penicillin on Italian pig farms. Our data highlight the need for monitoring the evolution of S. suis in the coming years.
Subject(s)
Aminoacyltransferases , Cephalosporins , Streptococcus suis , Animals , Swine , Penicillins/pharmacology , Penicillin-Binding Proteins/genetics , Streptococcus suis/genetics , Bacterial Proteins/genetics , Streptococcus pneumoniae/genetics , Serogroup , Aminoacyltransferases/genetics , Microbial Sensitivity Tests , Penicillin Resistance/genetics , Genomics , Ampicillin , Clone Cells , Anti-Bacterial Agents/pharmacologyABSTRACT
BACKGROUND: Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. RESULTS: In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. CONCLUSIONS: These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.
Subject(s)
Biofilms , Metabolomics , Streptococcus suis , Streptococcus suis/genetics , Streptococcus suis/metabolism , Biofilms/growth & development , Metabolic Networks and Pathways/genetics , Transcriptome , Gene Expression Profiling , Gene Expression Regulation, Bacterial , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Metabolome , MultiomicsABSTRACT
Streptococcus suis serotype 2 is a zoonotic agent that causes substantial economic losses to the swine industry and threatens human public health. Factors that contribute to its ability to cause disease are not yet fully understood. Glutamate dehydrogenase (GDH) is an enzyme found in living cells and plays vital roles in cellular metabolism. It has also been shown to affect pathogenic potential of certain bacteria. In this study, we constructed a S. suis serotype 2 GDH mutant (Δgdh) by insertional inactivation mediated by a homologous recombination event and confirmed loss of expression of GDH in the mutant by immunoblot and enzyme activity staining assays. Compared with the wild type (WT) strain, Δgdh displayed a different phenotype. It exhibited impaired growth in all conditions evaluated (solid and broth media, increased temperature, varying pH, and salinity) and formed cells of reduced size. Using a swine infection model, pigs inoculated with the WT strain exhibited fever, specific signs of disease, and lesions, and the strain could be re-isolated from the brain, lung, joint fluid, and blood samples collected from the infected pigs. Pigs inoculated with the Δgdh strain did not exhibit any clinical signs of disease nor histologic lesions, and the strain could not be re-isolated from any of the tissues nor body fluid sampled. The Δgdh also showed a decreased level of survival in pig blood. Taken together, these results suggest that the gdh is important in S. suis physiology and its ability to colonize, disseminate, and cause disease.
Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Swine , Animals , Humans , Virulence , Glutamate Dehydrogenase/genetics , Glutamate Dehydrogenase/metabolism , Streptococcus suis/genetics , Serogroup , Virulence Factors/genetics , Virulence Factors/metabolism , Swine Diseases/microbiology , Streptococcal Infections/veterinary , Streptococcal Infections/microbiologyABSTRACT
Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis.
Subject(s)
Antibodies, Bacterial , Bacterial Proteins , Disease Models, Animal , Mice, Inbred BALB C , Recombinant Proteins , Streptococcal Infections , Streptococcal Vaccines , Streptococcus suis , Vaccines, Subunit , Streptococcus suis/immunology , Streptococcus suis/genetics , Animals , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Mice , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Vaccines, Subunit/immunology , Vaccines, Subunit/genetics , Recombinant Proteins/immunology , Recombinant Proteins/genetics , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Streptococcal Vaccines/genetics , Serogroup , Cytokines/metabolism , Female , Membrane Proteins/immunology , Membrane Proteins/genetics , Immunity, Humoral , Antigens, Bacterial/immunology , Antigens, Bacterial/genetics , Swine Diseases/prevention & control , Swine Diseases/immunology , Swine Diseases/microbiology , Swine , Computational BiologyABSTRACT
Streptococcus suis is a zoonotic pathogen that causes a major health problem in the pig production industry worldwide. Spain is one of the largest pig producers in the world. This work aimed to investigate the genetic and phenotypic features of invasive S. suis isolates recovered in Spain. A panel of 156 clinical isolates recovered from 13 Autonomous Communities, representing the major pig producers, were analysed. MLST and serotyping analysis revealed that most isolates (61.6%) were assigned to ST1 (26.3%), ST123 (18.6%), ST29 (9.6%), and ST3 (7.1%). Interestingly, 34 new STs were identified, indicating the emergence of novel genetic lineages. Serotypes 9 (27.6%) and 1 (21.8%) prevailed, followed by serotypes 7 (12.8%) and 2 (12.2%). Analysis of 13 virulence-associated genes showed significant associations between ST, serotype, virulence patterns, and clinical features, evidencing particular virulence traits associated with genetic clusters. The pangenome was generated, and the core genome was distributed in 7 Bayesian groups where each group included a variable set of over- and under-represented genes of different categories. The study provides comprehensive data and knowledge to improve the design of new vaccines, antimicrobial treatments, and bacterial typing approaches.
Subject(s)
Streptococcus suis , Animals , Swine , Streptococcus suis/genetics , Spain/epidemiology , Bayes Theorem , Multilocus Sequence Typing/veterinary , Virulence , GenomicsABSTRACT
Streptococcus suis (S. suis) is an important porcine pathogen causing meningitis, arthritis, and septicemia. Serotypes 2 and 14 are the most common zoonotic ones worldwide, whereas serotypes 2, 9, and 7 are very important in pigs in Europe. To cause invasive infections S. suis needs to enter the bloodstream. Consequently, the immune response in blood represents an important line of defense and bacteremia plays a key role in the pathogenesis of invasive S. suis infections. We investigated the working hypothesis that S. suis strains of the same serotype but different clonal complex (CC) might exhibit substantial differences in the interaction with components of the immune system in porcine blood. The experimental design of this study includes comparative analysis of 8 virulent strains belonging to 4 serotypes with strains of the same serotype being genetically not closely related. Significant differences between two strains of the same serotype but different clonal complex were recorded in the flow cytometric analysis of association with different leukocytes for serotype 9 and 14. Our results demonstrate that the serotype 9 strain of CC94 shows significantly increased association with monocytes and survival in porcine blood of conventional piglets as well as a tendency towards decreased composition of C3 in plasma of these piglets in comparison to the serotype 9 strain of CC16. Correlation analysis of C3 deposition on the bacterial surface and survival in respective blood samples of 8-week-old piglets demonstrated a negative correlation indicating that C3 deposition is a crucial step to limit bacterial survival and proliferation of different S. suis pathotypes in the blood of these piglets. In summary, our results indicate that the capsule composition of a S. suis strain is not alone sufficient to determine association with leukocytes, activation of complement, induction of proinflammatory cytokines, oxidative burst, and bacterial survival in porcine blood. In this study, substantial differences in these host-pathogen interactions were observed between strains of the same serotype. Therefore, a more comprehensive characterization of the field isolates, including at least MLST analysis to determine the sequence type/clonal complex, is recommended.
Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Swine , Animals , Streptococcus suis/genetics , Monocytes , Multilocus Sequence Typing/veterinary , Serogroup , Granulocytes , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Swine Diseases/microbiologyABSTRACT
Streptococcus suis is a gram-positive bacterium that causes meningitis, septicemia, endocarditis, and other disorders in pigs and humans. We obtained 42 and 50 S. suis isolates from lesions of porcine endocarditis and palatine tonsils, respectively, of clinically healthy pigs in Japan; we then determined their sequence types (STs) by multilocus sequence typing (MLST), cps genotypes, serotypes, and presence of classical major virulence-associated marker genes (mrp, epf, and sly). The 42 isolates from endocarditis lesions were assigned to a limited number of STs and clonal complexes (CCs). On the other hand, the 50 isolates from tonsils were diverse in these traits and seemingly in the degree of virulence, suggesting that tonsils can accommodate a variety of S. suis isolates. The goeBURST full algorithm using tonsil isolates obtained in this study and those retrieved from the database showed that major CCs as well as many other clusters were composed of isolates originating from different countries, and some of the STs were very similar to each other despite the difference in country of origin. These findings indicate that S. suis with not only different but also similar mutations in the genome have survived in tonsils independently across different geographical locations. Therefore, unlike the lesions of endocarditis, the tonsils of pigs seemingly accommodate various S. suis lineages. The present study suggests that S. suis acquired its diversity by natural mutations during colonization and persistence in the tonsils of pigs.
Subject(s)
Endocarditis , Streptococcal Infections , Streptococcus suis , Swine Diseases , Humans , Swine , Animals , Multilocus Sequence Typing/veterinary , Palatine Tonsil/microbiology , Streptococcus suis/genetics , Streptococcal Infections/microbiology , Streptococcal Infections/veterinary , Swine Diseases/microbiology , Endocarditis/veterinaryABSTRACT
Streptococcus suis serotype 2 is a major swine pathogen and a zoonotic agent, causing meningitis in both swine and humans, responsible for substantial economic losses to the swine industry worldwide. The pathogenesis of infection and the role of bacterial cell wall components in virulence have not been fully elucidated. Lipoproteins, peptidoglycan, as well as lipoteichoic acids (LTA) have all been proposed to contribute to virulence. In the present study, the role of the LTA in the pathogenesis of the infection was evaluated through the characterisation of a mutant of the S. suis serotype 2 strain P1/7 lacking the LtaS enzyme, which mediates the polymerization of the LTA poly-glycerolphosphate chain. The ltaS mutant was confirmed to completely lack LTA and displayed significant morphological defects. Although the bacterial growth of this mutant was not affected, further results showed that LTA is involved in maintaining S. suis bacterial fitness. However, its role in the pathogenesis of the infection appears limited. Indeed, LTA presence reduces self-agglutination, biofilm formation and even dendritic cell activation, which are important aspects of the pathogenesis of the infection caused by S. suis. In addition, it does not seem to play a critical role in virulence using a systemic mouse model of infection.
Subject(s)
Rodent Diseases , Streptococcal Infections , Streptococcus suis , Swine Diseases , Humans , Mice , Animals , Swine , Serogroup , Cell Shape , Virulence , Streptococcal Infections/veterinary , Streptococcal Infections/microbiologyABSTRACT
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.
Subject(s)
Autovaccines , Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Streptococcus suis/immunology , Swine , Swine Diseases/prevention & control , Swine Diseases/microbiology , Swine Diseases/immunology , Streptococcal Infections/veterinary , Streptococcal Infections/prevention & control , Streptococcal Infections/immunology , Female , Immunity, Maternally-Acquired , Streptococcal Vaccines/immunology , Streptococcal Vaccines/administration & dosage , Serogroup , Vaccination/veterinaryABSTRACT
Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.
Subject(s)
Galactose , Quorum Sensing , Streptococcus suis , Streptococcus suis/physiology , Galactose/metabolism , Quorum Sensing/physiology , Virulence , Animals , Bacterial Capsules/metabolism , Lactones/metabolism , Streptococcal Infections/veterinary , Streptococcal Infections/microbiology , Streptococcal Infections/immunology , Homoserine/analogs & derivatives , Homoserine/metabolism , Polysaccharides, Bacterial/metabolismABSTRACT
Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method.
Subject(s)
Brain Infarction , Streptococcal Infections , Streptococcus suis , Humans , Streptococcus suis/isolation & purification , Male , Streptococcal Infections/microbiology , Streptococcal Infections/complications , Aged , Brain Infarction/microbiology , Brain Infarction/diagnostic imaging , Brain Infarction/complications , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/complications , Meningitis, Bacterial/drug therapy , Sepsis/microbiology , Sepsis/complications , Anti-Bacterial Agents/therapeutic useABSTRACT
Streptococcus suis (S. suis) is an important gram-positive pathogen and an emerging zoonotic pathogen that causes meningitis in swine and humans. Although several virulence factors have been characterized in S. suis, the underlying mechanisms of pathogenesis are not fully understood. In this study, we identified Zinc metalloproteinase C (ZmpC) probably as a critical virulence factor widely distributed in S. suis strains. ZmpC was identified as a critical facilitator in the development of bacterial meningitis, as evidenced by the detection of increased expression of TNF-α, IL-8, and matrix metalloprotease 9 (MMP-9). Subcellular localization analysis further revealed that ZmpC was localized to the cell wall surface and gelatin zymography analysis showed that ZmpC could cleave human MMP-9. Mice challenge demonstrated that ZmpC provided protection against S. suis CZ130302 (serotype Chz) and ZY05719 (serotype 2) infection. In conclusion, these results reveal that ZmpC plays an important role in promoting CZ130302 to cause mouse meningitis and may be a potential candidate for a S. suis CZ130302 vaccine.
Subject(s)
Meningitis, Bacterial , Serogroup , Streptococcal Infections , Streptococcus suis , Swine Diseases , Streptococcus suis/pathogenicity , Streptococcus suis/enzymology , Animals , Streptococcal Infections/veterinary , Streptococcal Infections/microbiology , Swine , Swine Diseases/microbiology , Mice , Meningitis, Bacterial/veterinary , Meningitis, Bacterial/microbiology , Female , Virulence Factors/metabolism , Virulence Factors/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Humans , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Mice, Inbred BALB C , Metalloendopeptidases/metabolism , Metalloendopeptidases/geneticsABSTRACT
Objective: The objective of this study was to monitor Streptococcus suis fecal shedding in nursery pigs on a farm with a history of S. suis disease involving serotypes 2 and 9. Animal and procedure: Four cohorts of pigs (n = 480) were monitored from weaning to end of nursery. Rectal swabs from 297 pigs were tested and S. suis serotypes 15 (n = 7), 31 (n = 3), or untypeable (n = 6) isolates were recovered from 16 (5.4%) pigs. Results: There was no significant association between S. suis fecal shedding and diarrhea. Streptococcus suis isolates recovered from pigs euthanized due to neurological signs or severe lameness were serotypes 9 (meninges) and 31 (tonsil) or untypeable (meninges, tonsil). Serotypes 9 (meninges, tonsil), 15 (spleen, tonsil), 16 (tonsil), 29 and 33 (nasal swabs), and untypeable (meninges, tonsil, and lung) isolates were identified in lame pigs. Conclusion and clinical relevance: These results suggest that feces may not be a source of infection for the S. suis serotypes producing disease in pigs; however, the association between S. suis fecal shedding and diarrhea needs further investigation. The coincidence of untypeable isolates in feces from healthy pigs and their isolation from meninges of pigs with neurological signs warrants further investigation to determine the molecular characteristics of those isolates.
Une enquête sur l'excrétion fécale des sérotypes de Streptococcus suis chez les porcelets en pouponnière. Objectif: L'objectif de cette étude était de surveiller l'excrétion fécale de Streptococcus suis chez des porcelets en pouponnière dans une ferme ayant des antécédents de maladie à S. suis impliquant les sérotypes 2 et 9. Animal et procédure: Quatre cohortes de porcs (n = 480) ont été suivies du sevrage jusqu'à la fin de la période en pouponnière. Des écouvillons rectaux provenant de 297 porcs ont été testés et des isolats de S. suis des sérotypes 15 (n = 7), 31 (n = 3) ou non-typables (n = 6) ont été récupérés chez 16 (5,4 %) porcs. Résultats: Il n'y avait aucune association significative entre l'excrétion fécale de S. suis et la diarrhée. Les isolats de S. suis récupérés chez des porcs euthanasiés en raison de signes neurologiques ou d'une boiterie sévère étaient de sérotypes 9 (méninges) et 31 (amygdales) ou non-typables (méninges, amygdales). Les sérotypes 9 (méninges, amygdales), 15 (rate, amygdales), 16 (amygdales), 29 et 33 (écouvillonnages nasaux) et des isolats non-typables (méninges, amygdales et poumons) ont été identifiés chez des porcs boitant. Conclusion et pertinence clinique: Ces résultats suggèrent que les matières fécales pourraient ne pas être une source d'infection pour les sérotypes de S. suis produisant des maladies chez les porcs; cependant, l'association entre l'excrétion fécale de S. suis et la diarrhée nécessite des recherches plus approfondies. La coïncidence d'isolats non-typables dans les selles de porcs sains et leur isolement dans les méninges de porcs présentant des signes neurologiques justifient des recherches plus approfondies pour déterminer les caractéristiques moléculaires de ces isolats.(Traduit par Dr Serge Messier).
Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Swine , Animals , Serogroup , Streptococcal Infections/veterinary , Diarrhea/veterinaryABSTRACT
Objective: Streptococcus suis is a major agent of disease in modern swine operations, linked to increased mortality, treatment costs, and secondary infections. Although it is ubiquitous in swine, only a fraction of pigs develop clinical disease. The goals of this study were to profile isolates obtained from diseased pigs in western Canada and to investigate potential associations with disease severity. Procedure: Isolates of S. suis (n = 128) from 75 diagnostic submission and 63 premises were paired with epidemiological surveys completed by submitting practitioners (n = 22). Whole-genome sequencing was used to type isolates. Results: The most prevalent serotypes identified were 1/2 (7.8%, 10/128), 2 (9.3%, 12/128), 3 (9.3%, 12/128), and 7 (7.8%, 10/128); and sequence types 28 (17%, 23/128) and 839 (14%, 19/128). There was no association between serotype or sequence type and organ source or barn location. Approximately 74% (14/19) of the premises had diseased animals colonized by > 1 S. suis serotype, but only 1 pig was simultaneously infected with multiple serotypes and sequence types. Serotype distribution from diseased pigs in western Canada differed from that of those in other geographic regions. Conclusion: Infection of diseased pigs by multiple serotypes should be considered when disease control strategies are implemented. No association between S. suis type and isolation organ was identified.
Le profil moléculaire et les caractéristiques épidémiologiques de Streptococcus suis isolés de porcs malades dans l'ouest du Canada révèlent une infection à sérotypes multiples : implications pour la maitrise de la maladie. Objectif: Streptococcus suis est un agent pathogène majeur dans les exploitations porcines modernes, lié à une mortalité accrue, aux coûts de traitement et aux infections secondaires. Bien qu'elle soit omniprésente chez le porc, seule une fraction des porcs développe une maladie clinique. Les objectifs de cette étude étaient de dresser le profil des isolats obtenus à partir de porcs malades dans l'ouest du Canada et d'étudier les associations potentielles avec la gravité de la maladie. Procédure: Des isolats de S. suis (n = 128) provenant de 75 soumissions pour diagnostic et de 63 sites ont été associés à des enquêtes épidémiologiques réalisées auprès des praticiens soumettant les échantillons (n = 22). Le séquençage du génome entier a été utilisé pour typer les isolats. Résultats: Les sérotypes les plus répandus identifiés étaient 1/2 (7,8 %, 10/128), 2 (9,3 %, 12/128), 3 (9,3 %, 12/128) et 7 (7,8 %, 10/128); et les types de séquence 28 (17 %, 23/128) et 839 (14 %, 19/128). Il n'y avait aucune association entre le sérotype ou le type de séquence et la source d'organes ou l'emplacement de la ferme. Environ 74 % (14/19) des exploitations abritaient des animaux malades colonisés par > 1 sérotype de S. suis, mais 1 seul porc était infecté simultanément par plusieurs sérotypes et types de séquences. La répartition des sérotypes chez les porcs malades de l'ouest du Canada différait de celle des porcs d'autres régions géographiques. Conclusion: L'infection des porcs malades par plusieurs sérotypes doit être envisagée lors de la mise en oeuvre de stratégies de maitrise de la maladie. Aucune association entre le type de S. suis et l'organe d'isolement n'a été identifiée.(Traduit par Dr Serge Messier).