scholarly journals Neoglycoconjugate of Tetrasaccharide Representing One Repeating Unit of the Streptococcus pneumoniae Type 14 Capsular Polysaccharide Induces the Production of Opsonizing IgG1 Antibodies and Possesses the Highest Protective Activity As Compared to Hexa- and Octasaccharide Conjugates

2017 ◽  
Vol 8 ◽  
Author(s):  
Ekaterina A. Kurbatova ◽  
Nelli K. Akhmatova ◽  
Elina A. Akhmatova ◽  
Nadezhda B. Egorova ◽  
Natalya E. Yastrebova ◽  
...  
2021 ◽  
Vol 20 (4) ◽  
pp. 59-65
Author(s):  
D. S. Vorobyev ◽  
M. M. Tokarskaya ◽  
S. A. Baranovskaya ◽  
E. A. Stefutushkina ◽  
O. M. Afanasyeva ◽  
...  

Introduction. Pneumococcal diseases remain relevant for the whole world. On the one hand, this is due to the high prevalence of pneumococcus and the other hand, the growth of antibiotic-resistant strains and the constant change of clinically significant serotypes of the pathogen.The aim of the research was to study of the protective activity of a mixture of pneumococcal antigens.Material and methods. we used preparations of a capsular polysaccharide (CPS) obtained from Streptococcus pneumoniae serotype 3; protein-containing fraction (PCF) obtained from an aqueous extract of cells of S. pneumoniae serotype 6B; recombinant pneumolysin (rPly). Mice were immunized intraperitoneally twice with an interval of 14 days with mixtures of bacterial antigens: CPS + PCF; CPS + rPly; PCF + rPly. To assess the protective activity of the studied drugs after double immunization animals were infected intraperitoneally with S. pneumoniae serotype 3. To study the effect of mixtures of bacterial preparations on the infectious process in the lungs immunized mice were infected with S. pneumoniae serotype 3. The humoral immune response was studied with IgG using the method of ELISA.Results. The CPS + rPly mixture protected mice from intraperitoneal infection with S. pneumoniae serotype 3 regardless of the infecting dose. Immunization with CPS + PCF or CPS + rPly mixtures influenced a significant decrease the number of seeded bacterial cells from lungs during the entire observation period (72 h) compared to the control. Administration of mixtures of bacterial antigens of CPS + PCF, CPS + rPly or PCF + rPly to animals led to a significant increase of the level of antibodies to all antigens, however, the highest levels of IgG were determined to PCF and rPly.Conclusion. The results obtained suggest that different antigenic drugs in mixtures affect different mechanisms of immunity activation.


mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Masahide Yano ◽  
Shruti Gohil ◽  
J. Robert Coleman ◽  
Catherine Manix ◽  
Liise-anne Pirofski

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.


1981 ◽  
Vol 59 (14) ◽  
pp. 2081-2085 ◽  
Author(s):  
Karin Leontein ◽  
Bengt Lindberg ◽  
Jörgen Lönngren

The capsular polysaccharide from Streptococcus pneumoniae type 12F is composed of D-glucosyl, D-galactosyl, 2-acetamido-2-deoxy-D-galactosyl, 2-acetamido-2,6-dideoxy-L-galactosyl, and 2-acetamido-2-deoxy-D-mannuronic acid residues in the proportions 2:1:1:1:1. The main structural evidence was adduced from nmr spectroscopy, methylation analysis, and specific degradations whereby it could be concluded that the polysaccharide is composed of hexasaccharide repeating-units having the structure:[Formula: see text]


mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Claudia Trappetti ◽  
Lauren J. McAllister ◽  
Austen Chen ◽  
Hui Wang ◽  
Adrienne W. Paton ◽  
...  

ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS ( S -ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae , sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.


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