scholarly journals Antibody Response Specific to the Capsular Polysaccharide Is Impaired in Streptococcus suis Serotype 2-Infected Animals

2014 ◽  
Vol 83 (1) ◽  
pp. 441-453 ◽  
Author(s):  
Cynthia Calzas ◽  
Paul Lemire ◽  
Gael Auray ◽  
Volker Gerdts ◽  
Marcelo Gottschalk ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Phenotypic Diversity ◽  
Streptococcus Suis ◽  
Content Type ◽  
Memory Response ◽  
Specific Memory ◽  
Versus Protein ◽  
Toll Like Receptor 2 ◽  
Encapsulated Bacteria

Streptococcus suisserotype 2 is an extracellular encapsulated bacterium that causes severe septicemia and meningitis in swine and humans. Albeit crucial in the fight against encapsulated bacteria, the nature of the capsular polysaccharide (CPS)-specific antibody (Ab) response duringS. suistype 2 infection is unknown. We compared for the first time the features of CPS-specific versus protein-specific Ab responses during experimental infections with live virulentS. suistype 2 in mice. The primary protein-specific Ab response was dominated by both type 1 and 2 IgG subclasses, whereas IgM titers were more modest. The secondary protein-specific Ab response showed all of the features of a memory response with faster kinetics and boosted the titers of all Ig isotypes. In contrast, the primary CPS-specific Ab response was either inexistent or had titers only slightly higher than those in noninfected animals and was essentially composed of IgM. A poor CPS-specific memory response was observed, with only a moderate boost in IgM titers and no IgG. Both protein- and CPS-specific Ab responses were Toll-like receptor 2 independent. By usingS. suistype 2 strains of European or North American origin, the poor CPS-specific Ab response was demonstrated to be independent of the genotypic/phenotypic diversity of the strain within serotype 2. Finally, the CPS-specific Ab response was also impaired and lacked isotype switching inS. suis-infected pigs, the natural host of the bacterium. The better resistance of preinfected animals to reinfection with the same strain ofS. suistype 2 might thus more likely be related to the development of a protein rather than CPS Ab response.

scholarly journals Streptococcus suis Capsular Polysaccharide Inhibits Phagocytosis through Destabilization of Lipid Microdomains and Prevents Lactosylceramide-Dependent Recognition

2011 ◽  
Vol 80 (2) ◽  
pp. 506-517 ◽  
Author(s):  
Mathieu Houde ◽  
Marcelo Gottschalk ◽  
Fleur Gagnon ◽  
Marie-Rose Van Calsteren ◽  
Mariela Segura
Keyword(s):  
Molecular Mechanisms ◽  
Capsular Polysaccharide ◽  
Streptococcus Suis ◽  
No Production ◽  
Lipid Microdomains ◽  
Content Type ◽  
Swine Pathogen ◽  
Latex Beads ◽  
Covalently Linked

ABSTRACTStreptococcus suistype 2 is a major swine pathogen and a zoonotic agent, causing meningitis in both swine and humans.S. suisinfects the host through the respiratory route, reaches the bloodstream, and persists until breaching into the central nervous system. The capsular polysaccharide (CPS) ofS. suistype 2 is considered a key virulence factor of the bacteria. Though CPS allowsS. suisto adhere to the membrane of cells of the immune system, it provides protection against phagocytosis. In fact, nonencapsulated mutants are easily internalized and killed by macrophages and dendritic cells. The objective of this work was to study the molecular mechanisms by which the CPS ofS. suisprevents phagocytosis. By using latex beads covalently linked with purified CPS, it was shown that CPS itself was sufficient to inhibit entry of both latex beads and bystander fluorescent beads into macrophages. Upon contact with macrophages, encapsulatedS. suiswas shown to destabilize lipid microdomains at the cell surface, to block nitric oxide (NO) production during infection, and to prevent lactosylceramide accumulation at the phagocytic cup during infection. In contrast, the nonencapsulated mutant was easily internalized via lipid rafts, in a filipin-sensitive manner, leading to lactosylceramide recruitment and strong NO production. This is the first report to identify a role for CPS in lipid microdomain stability and to recognize an interaction betweenS. suisand lactosylceramide in phagocytes.

scholarly journals Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

2016 ◽  
Vol 84 (7) ◽  
pp. 2059-2075 ◽  
Author(s):  
Guillaume Goyette-Desjardins ◽  
Cynthia Calzas ◽  
Tze Chieh Shiao ◽  
Axel Neubauer ◽  
Jennifer Kempker ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Functional Activity ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Streptococcus Suis ◽  
Vaccine Strategy ◽  
Content Type ◽  
Glycoconjugate Vaccine

Streptococcus suisserotype 2 is an encapsulated bacterium and one of the most important bacterial pathogens in the porcine industry. Despite decades of research for an efficient vaccine, none is currently available. Based on the success achieved with other encapsulated pathogens, a glycoconjugate vaccine strategy was selected to elicit opsonizing anti-capsular polysaccharide (anti-CPS) IgG antibodies. In this work, glycoconjugate prototypes were prepared by couplingS. suistype 2 CPS to tetanus toxoid, and the immunological features of the postconjugation preparations were evaluatedin vivo. In mice, experiments evaluating three different adjuvants showed that CpG oligodeoxyribonucleotide (ODN) induces very low levels of anti-CPS IgM antibodies, while the emulsifying adjuvants Stimune and TiterMax Gold both induced high levels of IgGs and IgM. Dose-response trials comparing free CPS with the conjugate vaccine showed that free CPS is nonimmunogenic independently of the dose used, while 25 μg of the conjugate preparation was optimal in inducing high levels of anti-CPS IgGs postboost. With an opsonophagocytosis assay using murine whole blood, sera from immunized mice showed functional activity. Finally, the conjugate vaccine showed immunogenicity and induced protection in a swine challenge model. When conjugated and administered with emulsifying adjuvants,S. suistype 2 CPS is able to induce potent IgM and isotype-switched IgGs in mice and pigs, yielding functional activityin vitroand protection against a lethal challengein vivo, all features of a T cell-dependent response. This study represents a proof of concept for the potential of glycoconjugate vaccines in veterinary medicine applications against invasive bacterial infections.

scholarly journals Comparative Study of Immunogenic Properties of Purified Capsular Polysaccharides from Streptococcus suis Serotypes 3, 7, 8, and 9: the Serotype 3 Polysaccharide Induces an Opsonizing IgG Response

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Guillaume Goyette-Desjardins ◽  
Jean-Philippe Auger ◽  
Dominic Dolbec ◽  
Evgeny Vinogradov ◽  
Masatoshi Okura ◽  
...  
Keyword(s):  
Immune System ◽  
Secondary Infection ◽  
Streptococcus Suis ◽  
Biochemical Properties ◽  
Divergent Evolution ◽  
Effective Vaccine ◽  
Capsular Polysaccharides ◽  
Content Type ◽  
Chemokine Ligand ◽  
Encapsulated Bacteria

ABSTRACT Streptococcus suis is an encapsulated bacterium and one of the most important swine pathogens and a zoonotic agent for which no effective vaccine exists. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. In addition to the previously known serotypes 2 and 14, which are nonimmunogenic, we have recently purified and described the CPS structures for serotypes 1, 1/2, 3, 7, 8, and 9. Here, we aimed to elucidate how these new structurally diverse CPSs interact with the immune system to generate anti-CPS antibody responses. CPS-stimulated dendritic cells produced significant levels of C–C motif chemokine ligand 3 (CCL3), partially via Toll-like receptor 2 (TLR2)- and myeloid differentiation factor 88-dependent pathways, and CCL2, via TLR-independent mechanisms. Mice immunized with purified serotype 3 CPS adjuvanted with TiterMax Gold produced an opsonizing IgG response, whereas other CPSs or adjuvants were negative. Mice hyperimmunized with heat-killed S. suis serotypes 3 and 9 both produced anti-CPS type 1 IgGs, whereas serotypes 7 and 8 remained negative. Also, mice infected with sublethal doses of S. suis serotype 3 produced primary anti-CPS IgM and IgG responses, of which only IgM were boosted after a secondary infection. In contrast, mice sublethally infected with S. suis serotype 9 produced weak anti-CPS IgM and IgG responses following a secondary infection. This study provides important information on the divergent evolution of CPS serotypes with highly different structural and/or biochemical properties within S. suis and their interaction with the immune system.

scholarly journals Novel Capsular Polysaccharide Loci and New Diagnostic Tools for High-Throughput Capsular Gene Typing in Streptococcus suis

2016 ◽  
Vol 82 (24) ◽  
pp. 7102-7112 ◽  
Author(s):  
Xiaotong Qiu ◽  
Xuemei Bai ◽  
Ruiting Lan ◽  
Han Zheng ◽  
Jianguo Xu
Keyword(s):  
Genetic Information ◽  
Capsular Polysaccharide ◽  
Detection System ◽  
Cost Effective ◽  
Streptococcus Suis ◽  
Epidemiological Studies ◽  
Diagnostic Tools ◽  
Genetic Characteristics ◽  
Content Type ◽  
Gene Typing

ABSTRACTStreptococcus suisis an important pathogen of pigs and may cause serious disease in humans. Serotyping is an important tool for detection and epidemiological studies ofS. suis. Thirty-three reference serotypes and nine novelcpsloci (NCLs) are recognized inS. suis. To gain a better understanding of the prevalence and genetic characteristics of NCLs, we investigated the serotype identity of 486 isolates isolated between 2013 and 2015 in China by capsular gene typing methods. Two hundred seventy-six isolates carried NCLs belonging to 16 groups, 8 of which appear to have not been reported previously. These isolates showed autoagglutination, polyagglutination, or nonagglutination with reference antisera and thus were nonserotypeable. Almost all isolates carrying the unknown NCLs were encapsulated, with various capsular thicknesses, indicating that they are most likely novel serotypes. To simultaneously identify the currently recognized 17 NCLs, an 18-plex detection system using the Luminex xTAG universal array technology was developed. Our data also provide valuable genetic information for monitoring the variations within NCLs by investigating the genetic characteristics of different subtypes within NCLs.IMPORTANCENonserotypeableStreptococcus suisisolates have been reported in many studies, and 9 novelcpsloci (NCLs) have already been identified in nonserotypeable isolates. Moreover, novelcpsloci are continually being found. The main purpose of this study was to investigate the prevalence and characteristics of NCLs inS. suisisolates recovered between 2013 and 2015 in China. This study provides valuable genetic information for monitoring the variations within NCLs. Meanwhile, a fast and cost-effective 18-plex detection system that can simultaneously identify the currently recognized 17 NCLs was developed in this study. This system will serve as a valuable tool for detecting known and identifying additional novelcpsloci among nonserotypeableS. suisisolates.

scholarly journals Sequence Elements Upstream of the Core Promoter Are Necessary for Full Transcription of the Capsule Gene Operon in Streptococcus pneumoniae Strain D39

2015 ◽  
Vol 83 (5) ◽  
pp. 1957-1972 ◽  
Author(s):  
Zhensong Wen ◽  
Odeniel Sertil ◽  
Yongxin Cheng ◽  
Shanshan Zhang ◽  
Xue Liu ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Core Promoter ◽  
Virulent Strain ◽  
Bacterial Pathogen ◽  
Content Type ◽  
The Core ◽  
Sequence Elements ◽  
Almost All

Streptococcus pneumoniaeis a major bacterial pathogen in humans. Its polysaccharide capsule is a key virulence factor that promotes bacterial evasion of human phagocytic killing. WhileS. pneumoniaeproduces at least 94 antigenically different types of capsule, the genes for biosynthesis of almost all capsular types are arranged in the same locus. The transcription of the capsular polysaccharide (cps) locus is not well understood. This study determined the transcriptional features of thecpslocus in the type 2 virulent strain D39. The initial analysis revealed that thecpsgenes are cotranscribed from a major transcription start site at the −25 nucleotide (G) upstream ofcps2A, the first gene in the locus. Using unmarked chromosomal truncations and a luciferase-based transcriptional reporter, we showed that the full transcription of thecpsgenes not only depends on the core promoter immediately upstream ofcps2A, but also requires additional elements upstream of the core promoter, particularly a 59-bp sequence immediately upstream of the core promoter. Unmarked deletions of these promoter elements in the D39 genome also led to significant reduction in CPS production and virulence in mice. Lastly, commoncpsgene (cps2ABCD) mutants did not show significant abnormality incpstranscription, although they produced significantly less CPS, indicating that the CpsABCD proteins are involved in the encapsulation ofS. pneumoniaein a posttranscriptional manner. This study has yielded important information on the transcriptional characteristics of thecpslocus inS. pneumoniae.

scholarly journals Streptococcal infection in young pigs. V. An immunogenic polysaccharide from Streptococcus suis type 2 with particular reference to vaccination against streptococcal meningitis in pigs

1980 ◽  
Vol 85 (2) ◽  
pp. 275-285 ◽  
Author(s):  
S. D. Elliott ◽  
Felicity Clifton-Hadley ◽  
Joseph Tai
Keyword(s):  
Capsular Polysaccharide ◽  
Streptococcal Infection ◽  
Streptococcus Suis ◽  
Booster Injection ◽  
Young Pigs ◽  
Unvaccinated Control ◽  
Streptococcal Meningitis ◽  
Late Bleeding

SUMMARYOf 17 pigs vaccinated with Streptococcus suis type-2 capsular polysaccharide plus Freund's Incomplete Adjuvant, all developed opsonizing antibody against Str. suis type 2. Of 14 pigs vaccinated with type-2 polysaccharide alone, 4 (possibly 6) developed opsonizing antibody. It is possible that some pigs vaccinated with polysaccharide plus Freund's Incomplete Adjuvant developed opsonizing antibody in response to a ‘booster’ injection of polysaccharide alone. Of 21 unvaccinated control pigs, late bleeding from 3 showed opsonizing activity against Str. suis type 2.

Detection of antibodies against Streptococcus suis capsular type 2 using a purified capsular polysaccharide antigen-based indirect ELISA

1996 ◽  
Vol 52 (1-2) ◽  
pp. 113-125 ◽  
Author(s):  
E. Martin del Campo Sepúlveda ◽  
E. Altman ◽  
M. Kobisch ◽  
S. D'Allaire ◽  
M. Gottschalk
Keyword(s):  
Capsular Polysaccharide ◽  
Indirect Elisa ◽  
Streptococcus Suis ◽  
Capsular Type ◽  
Polysaccharide Antigen

scholarly journals Eight Novel Capsular Polysaccharide Synthesis Gene Loci Identified in Nontypeable Streptococcus suis Isolates

2015 ◽  
Vol 81 (12) ◽  
pp. 4111-4119 ◽  
Author(s):  
Han Zheng ◽  
Shaobo Ji ◽  
Zhijie Liu ◽  
Ruiting Lan ◽  
Ying Huang ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Streptococcus Suis ◽  
Diagnostic Tools ◽  
Genetic Characteristics ◽  
Content Type ◽  
Transmission Electron ◽  
Polysaccharide Synthesis ◽  
Serious Disease ◽  
Dependent Pathway ◽  
Insight Into

ABSTRACTStreptococcus suisis an important pathogen of pigs and may cause serious disease in humans. Serotyping is one of the important diagnostic tools and is used for the epidemiological study ofS. suis. NontypeableS. suisstrains have been reported in many studies; however, the capsular polysaccharide (CPS) synthesiscpsloci of nontypeable strains have not been analyzed. In this study, we investigated the genetic characteristics ofcpsloci in 78 nontypeable strains isolated from healthy pigs. Eight novelcpsloci (NCLs) were found, and all of them were located between theorfZ-orfXregion and theglfgene. All NCLs possess thewzyandwzxgenes, strongly suggesting that the CPSs of these NCLs were synthesized using the Wzx/Wzy-dependent pathway. Thecpsgenes found in the 78 isolates were assigned to 96 homology groups (HGs), 55 of which were NCL specific. The encapsulation of the 78 isolates was also examined using transmission electron microscopy. Fifty-three isolates were found to have a capsule, and these were of varied thicknesses. Our data enhance our understanding of thecpsgene cluster diversity of nontypeableS. suisstrains and provide insight into the evolution of theS. suiscapsular genes.

scholarly journals Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri

2016 ◽  
Vol 84 (12) ◽  
pp. 3328-3337 ◽  
Author(s):  
Chenlin Pei ◽  
Chao Zhao ◽  
An-Jiang Wang ◽  
Anya X. Fan ◽  
Viktoriya Grinchuk ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Critical Role ◽  
Nematode Infection ◽  
Intestinal Smooth Muscle ◽  
Heligmosomoides Polygyrus ◽  
Content Type ◽  
Memory Response ◽  
Worm Expulsion ◽  
Interleukin 25

Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb , were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri . Genetic deletion of IL-25 (IL-25 −/− ) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25 −/− mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25 −/− mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.

scholarly journals Genetic Analysis of Capsular Polysaccharide Synthesis Gene Clusters from All Serotypes of Streptococcus suis: Potential Mechanisms for Generation of Capsular Variation

2013 ◽  
Vol 79 (8) ◽  
pp. 2796-2806 ◽  
Author(s):  
Masatoshi Okura ◽  
Daisuke Takamatsu ◽  
Fumito Maruyama ◽  
Takashi Nozawa ◽  
Ichiro Nakagawa ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Single Gene ◽  
Streptococcus Suis ◽  
Gene Clusters ◽  
Small Scale ◽  
Specific Gene ◽  
Chromosomal Locus ◽  
Content Type ◽  
Comprehensive Information ◽  
Genes Encoding

ABSTRACTStreptococcus suisstrains are classified into 35 serotypes on the basis of the antigenicity of their capsular polysaccharides (CPs). CP synthesis genes are known to be clustered on the chromosome (cpsgene cluster). The entirecpsgene clusters ofS. suishave so far been sequenced in 15 serotypes and found to be located betweenorfZandaroA. In this study, to provide comprehensive information aboutS. suisCPs, we sequenced the entirecpsgene clusters of the remaining serotypes and analyzed the complete set ofS. suiscpsgene clusters. Among the 35cpsgene clusters, 22 were located betweenorfZandaroA, whereas the other 13 were flanked by other gene(s) on the chromosomes, and the chromosomal locus was classified into five patterns. By clustering analysis, the predicted products ofcpsgenes found in the 35 serotypes were assigned into 291 homology groups, and all serotypes possessed a serotype-specific gene, except for serotypes 1, 2, 1/2, and 14. Because of the presence of genes encoding flippase (wzx) and polymerase (wzy), CPs of all serotypes were thought to be synthesized by the Wzx/Wzy pathway. Our data also implied the possibility of the transfer of the entire or partialcpsgene clusters amongS. suisstrains, as well as the influence of spontaneous mutations in a single gene or a few genes on the antigenicity of some serotypes. Accumulation of these gene transfers and small-scale mutations may have generated the antigenic diversity ofS. suisCPs.

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