scholarly journals Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5

2009 ◽  
Vol 206 (8) ◽  
pp. 1691-1699 ◽  
Author(s):  
Aaron F. Carlin ◽  
Yung-Chi Chang ◽  
Thomas Areschoug ◽  
Gunnar Lindahl ◽  
Nancy Hurtado-Ziola ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Protein Tyrosine Phosphatases ◽  
Human Leukocyte ◽  
Bacterial Survival ◽  
Independent Manner ◽  
Lectin Receptor ◽  
Β Protein ◽  
Group B

Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall–anchored β protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS β protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.

scholarly journals Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3333-3336 ◽  
Author(s):  
Aaron F. Carlin ◽  
Satoshi Uchiyama ◽  
Yung-Chi Chang ◽  
Amanda L. Lewis ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Molecular Mimicry ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Extracellular Dna ◽  
Dependent Manner ◽  
Bacterial Survival ◽  
Amino Terminal ◽  
Group B ◽  
In Cis

Abstract Human neutrophil Siglec-9 is a lectin that recognizes sialic acids (Sias) via an amino-terminal V-set Ig domain and possesses tyrosine-based inhibitory motifs in its cytoplasmic tail. We hypothesized that Siglec-9 recognizes host Sias as “self,” including in cis interactions with Sias on the neutrophil's own surface, thereby dampening unwanted neutrophil reactivity. Here we show that neutrophils presented with immobilized multimerized Siaα2-3Galβ1-4GlcNAc units engage them in trans via Siglec-9. The sialylated capsular polysaccharide of group B Streptococcus (GBS) also presents terminal Siaα2-3Galβ1-4GlcNAc units, and similarly engages neutrophil Siglec-9, dampening neutrophil responses in a Sia- and Siglec-9–dependent manner. Reduction in the neutrophil oxidative burst, diminished formation of neutrophil extracellular DNA traps, and increased bacterial survival are also facilitated by GBS sialylated capsular polysaccharide interactions with Siglec-9. Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion.

Synthesis of a disialylated hexasaccharide of Type VIII Group B Streptococcus capsular polysaccharide

1999 ◽  
Vol 319 (1-4) ◽  
pp. 1-16 ◽  
Author(s):  
Eva Eichler ◽  
Harold J. Jennings ◽  
Michel Gilbert ◽  
Dennis M. Whitfield
Keyword(s):  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Type Viii ◽  
Group B

scholarly journals NeuA Sialic Acid O-Acetylesterase Activity Modulates O-Acetylation of Capsular Polysaccharide in Group B Streptococcus

2007 ◽  
Vol 282 (38) ◽  
pp. 27562-27571 ◽  
Author(s):  
Amanda L. Lewis ◽  
Hongzhi Cao ◽  
Silpa K. Patel ◽  
Sandra Diaz ◽  
Wesley Ryan ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Site Directed Mutagenesis ◽  
Synthetase Activity ◽  
Bacterial Surface ◽  
Acetylneuraminic Acid ◽  
Single Polypeptide ◽  
Group B

Group B Streptococcus (GBS) is a common cause of neonatal sepsis and meningitis. A major GBS virulence determinant is its sialic acid (Sia)-capped capsular polysaccharide. Recently, we discovered the presence and genetic basis of capsular Sia O-acetylation in GBS. We now characterize a GBS Sia O-acetylesterase that modulates the degree of GBS surface O-acetylation. The GBS Sia O-acetylesterase operates cooperatively with the GBS CMP-Sia synthetase, both part of a single polypeptide encoded by the neuA gene. NeuA de-O-acetylation of free 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) was enhanced by CTP and Mg2+, the substrate and co-factor, respectively, of the N-terminal GBS CMP-Sia synthetase domain. In contrast, the homologous bifunctional NeuA esterase from Escherichia coli K1 did not display cofactor dependence. Further analyses showed that in vitro, GBS NeuA can operate via two alternate enzymatic pathways: de-O-acetylation of Neu5,9Ac2 followed by CMP activation of Neu5Ac or activation of Neu5,9Ac2 followed by de-O-acetylation of CMP-Neu5,9Ac2. Consistent with in vitro esterase assays, genetic deletion of GBS neuA led to accumulation of intracellular O-acetylated Sias, and overexpression of GBS NeuA reduced O-acetylation of Sias on the bacterial surface. Site-directed mutagenesis of conserved asparagine residue 301 abolished esterase activity but preserved CMP-Sia synthetase activity, as evidenced by hyper-O-acetylation of capsular polysaccharide Sias on GBS expressing only the N301A NeuA allele. These studies demonstrate a novel mechanism regulating the extent of capsular Sia O-acetylation in intact bacteria and provide a genetic strategy for manipulating GBS O-acetylation in order to explore the role of this modification in GBS pathogenesis and immunogenicity.

scholarly journals Preventing Bacterial Infections with Pilus-Based Vaccines: the Group B Streptococcus Paradigm

2009 ◽  
Vol 199 (1) ◽  
pp. 108-115 ◽  
Author(s):  
Immaculada Margarit ◽  
Cira Daniela Rinaudo ◽  
Cesira L. Galeotti ◽  
Domenico Maione ◽  
Claudia Ghezzo ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Group B Streptococcus ◽  
Group B

Structural elucidation of the novel type VII group B Streptococcus capsular polysaccharide by high resolution NMR spectroscopy

1995 ◽  
Vol 277 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Grigorij Kogan ◽  
Jean-Robert Brisson ◽  
Dennis L. Kasper ◽  
Christina von Hunolstein ◽  
Graziella Orefici ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
High Resolution ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Structural Elucidation ◽  
The Novel ◽  
High Resolution Nmr ◽  
Group B

scholarly journals Molecular epidemiology of infections caused by group B Streptococcus in pregnant women and newborns, and development of preventive vaccines

2018 ◽  
Vol 67 (5) ◽  
pp. 62-73
Author(s):  
Vasilisa A. Vasilyeva ◽  
Elena V. Shipitsyna ◽  
Kira V. Shalepo ◽  
Alevtina M. Savicheva
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Group B Streptococcus ◽  
Epidemiological Data ◽  
Group B Streptococci ◽  
Group B ◽  
Sequence Types ◽  
Experimental Immunization ◽  
Selection Of

Hypothesis/aims of study. The present analysis was undertaken to summarize current knowledge about molecular properties of group B streptococci (GBS), emphasizing potential targets of vaccines against neonatal GBS infection. Study design, materials, and methods. This review is based on articles published mainly in the last ten years. Results. Epidemiological data on serotypes, multilocus sequence types, clonal complexes of GBS and their relationship are presented. Genetic events in GBS populations indicate significant obstacles to vaccine development. We described key properties of major GBS virulence factors, such as capsular polysaccharide, pili, and cell adhesion molecules, as well as results of experimental immunization on their basis. Conclusion. The population of invasive GBS strains is molecularly and genetically heterogeneous, which complicates selection of vaccine targets. Capsular switching, a low level of immunogenicity and variability of population composition are the most important factors that necessitate the accumulation and monitoring of molecular epidemiological data.

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