scholarly journals Group B Streptococcus Engages an Inhibitory Siglec through Sialic Acid Mimicry to Blunt Innate Immune and Inflammatory Responses In Vivo

2014 ◽  
Vol 10 (1) ◽  
pp. e1003846 ◽  
Author(s):  
Yung-Chi Chang ◽  
Joshua Olson ◽  
Federico C. Beasley ◽  
Christine Tung ◽  
Jiquan Zhang ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Inflammatory Responses ◽  
Group B Streptococcus ◽  
Innate Immune ◽  
Group B

scholarly journals O-Acetylation of sialic acid on Group B Streptococcus inhibits neutrophil suppression and virulence

2010 ◽  
Vol 428 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Shannon Weiman ◽  
Satoshi Uchiyama ◽  
Feng-Ying C. Lin ◽  
Donald Chaffin ◽  
Ajit Varki ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Group B Streptococcus ◽  
In Vivo Assays ◽  
Group B

GBS (Group B Streptococcus) requires capsular Sia (sialic acid) for virulence and partially modifies this sugar by O-acetylation. In the present paper we describe serotype-specific patterns of GBS Sia O-acetylation that can be manipulated by genetic and biochemical means. In vitro and in vivo assays demonstrate that this subtle modification attenuates GBS Sia-mediated neutrophil suppression and animal virulence.

scholarly journals MyD88-Dependent Signaling Affects the Development of Meningococcal Sepsis by Nonlipooligosaccharide Ligands

2006 ◽  
Vol 74 (6) ◽  
pp. 3538-3546 ◽  
Author(s):  
Laura Plant ◽  
Hong Wan ◽  
Ann-Beth Jonsson
Keyword(s):  
Inflammatory Responses ◽  
Innate Immune ◽  
Meningococcal Sepsis ◽  
Wild Type ◽  
Microbial Infections ◽  
In The Wild ◽  
Myeloid Differentiation Factor ◽  
Dependent Pathway ◽  
Meningococcal Strain

ABSTRACT The Toll-like receptors (TLRs) and the adaptor myeloid differentiation factor 88 (MyD88) are important in the innate immune defenses of the host to microbial infections. Meningococcal ligands signaling via TLRs control inflammatory responses, and stimulation can result in fulminant meningococcal sepsis. In this study, we show that the responses to nonlipooligosaccharide (non-LOS) ligands of meningococci are MyD88 dependent. An isogenic LOS-deficient mutant of the serogroup C meningococcal strain FAM20 caused fatal disease in wild type C57BL/6 mice that was not observed in MyD88−/− mice. Fatality correlated with high proinflammatory cytokine and C5a levels in serum, high neutrophil numbers in blood, and increased bacteremia at 24 h postinfection in the wild-type mice. Infection with the parent strain FAM20 resulted in fatality in 100% of the wild-type mice and 50% of the MyD88−/− mice. We conclude that both LOS and another neisserial ligand cause meningococcal sepsis in an in vivo mouse model and confirm that meningococcal LOS can act via both the MyD88- dependent and -independent pathways, while the non-LOS meningococcal ligand(s) acts only via the MyD88-dependent pathway.

scholarly journals Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia Beyrich ◽  
Jürgen Löffler ◽  
Anna Kobsar ◽  
Christian P. Speer ◽  
Susanne Kneitz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Group B Streptococcus ◽  
Gene Array ◽  
Neonatal Morbidity ◽  
Innate Immune ◽  
Human Coronary Artery ◽  
Chemotactic Protein ◽  
Early Onset Sepsis ◽  
Group B

Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocyte chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.

scholarly journals Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: Phenotypic and functional impact

Glycobiology ◽  
2009 ◽  
Vol 19 (11) ◽  
pp. 1204-1213 ◽  
Author(s):  
S. Weiman ◽  
S. Dahesh ◽  
A. F Carlin ◽  
A. Varki ◽  
V. Nizet ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Group B Streptococcus ◽  
Biochemical Modulation ◽  
Functional Impact ◽  
Group B

scholarly journals Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans

2018 ◽  
Vol 104 (4) ◽  
pp. 1187-1199 ◽  
Author(s):  
Ahmed Iqbal ◽  
Lynne R Prince ◽  
Peter Novodvorsky ◽  
Alan Bernjak ◽  
Mark R Thomas ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Immune System ◽  
Innate Immune System ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Platelet Reactivity ◽  
Innate Immune ◽  
Endotoxin Challenge ◽  
Intermediate Monocytes

Abstract Context Hypoglycemia is emerging as a risk for cardiovascular events in diabetes. We hypothesized that hypoglycemia activates the innate immune system, which is known to increase cardiovascular risk. Objective To determine whether hypoglycemia modifies subsequent innate immune system responses. Design and Setting Single-blinded, prospective study of three independent parallel groups. Participants and Interventions Twenty-four healthy participants underwent either a hyperinsulinemic-hypoglycemic (2.5 mmol/L), euglycemic (6.0 mmol/L), or sham-saline clamp (n = 8 for each group). After 48 hours, all participants received low-dose (0.3 ng/kg) intravenous endotoxin. Main Outcome Measures We studied in-vivo monocyte mobilization and monocyte-platelet interactions. Results Hypoglycemia increased total leukocytes (9.98 ± 1.14 × 109/L vs euglycemia 4.38 ± 0.53 × 109/L, P < 0.001; vs sham-saline 4.76 ± 0.36 × 109/L, P < 0.001) (mean ± SEM), mobilized proinflammatory intermediate monocytes (42.20 ± 7.52/μL vs euglycemia 20.66 ± 3.43/μL, P < 0.01; vs sham-saline 26.20 ± 3.86/μL, P < 0.05), and nonclassic monocytes (36.16 ± 4.66/μL vs euglycemia 12.72 ± 2.42/μL, P < 0.001; vs sham-saline 19.05 ± 3.81/μL, P < 0.001). Following hypoglycemia vs euglycemia, platelet aggregation to agonist (area under the curve) increased (73.87 ± 7.30 vs 52.50 ± 4.04, P < 0.05) and formation of monocyte-platelet aggregates increased (96.05 ± 14.51/μL vs 49.32 ± 6.41/μL, P < 0.05). Within monocyte subsets, hypoglycemia increased aggregation of intermediate monocytes (10.51 ± 1.42/μL vs euglycemia 4.19 ± 1.08/μL, P < 0.05; vs sham-saline 3.81± 1.42/μL, P < 0.05) and nonclassic monocytes (9.53 ± 1.08/μL vs euglycemia 2.86 ± 0.72/μL, P < 0.01; vs sham-saline 3.08 ± 1.01/μL, P < 0.05), with platelets compared with controls. Hypoglycemia led to greater leukocyte mobilization in response to subsequent low-dose endotoxin challenge (10.96 ± 0.97 vs euglycemia 8.21 ± 0.85 × 109/L, P < 0.05). Conclusions Hypoglycemia mobilizes monocytes, increases platelet reactivity, promotes interaction between platelets and proinflammatory monocytes, and potentiates the subsequent immune response to endotoxin. These changes may contribute to increased cardiovascular risk observed in people with diabetes.

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 Seroepidemiology of group B streptococcus type II antibody specificity

1988 ◽  
Vol 101 (2) ◽  
pp. 347-354 ◽  
Author(s):  
B. M. Gray ◽  
D. G. Pritchard ◽  
J. D. Springfield ◽  
R. J. Benak ◽  
H. C. Dillon
Keyword(s):  
Sialic Acid ◽  
Antibody Level ◽  
Specific Antibody ◽  
Group B Streptococcus ◽  
Antibody Specificity ◽  
Type Ii ◽  
Elisa System ◽  
Human Antibodies ◽  
Group B

SUMMARYThe specificity of human antibodies for the two major sidechain determinants of the type II group B streptococcal (GBS) polysaccharide was examined in 90 pairs of maternal and cord sera. Using an ELISA system, total antibody was measured against the complete (sialylated) type II antigen and the proportion of antibody against the galactose determinant was estimated by inhibition with free β–methylgalactopyranosided. Mothers colonized by type II or by other GBS types had higher levels of total specific antibody (means, 33 and 4–7 µg/ml, respectively) than those not colonized (mean, 2–2 µg/ml). Cord sera averaged 1–2 µg/ml lower than maternal sera. Colonization with GBS was also associated with higher levels against the galactose determinant (mean, 1.5&µg/ml, compared to 0–7µg/ml for those not colonized). The distribution of specificities favoured antibodies against the sialic acid determinant in maternal but not cord sera. Specificity as well as antibody level may play a role in the epidemiology of GBS type II.

Variability of neuD transcription levels and capsular sialic acid expression among serotype III group B Streptococcus strains

Microbiology ◽  
2011 ◽  
Vol 157 (12) ◽  
pp. 3282-3291 ◽  
Author(s):  
Marie-Frédérique Lartigue ◽  
Agnès Fribourg Poulard ◽  
Rim Al Safadi ◽  
Hélène Pailhories ◽  
Anne-Sophie Domelier-Valentin ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Sialic Acid ◽  
Growth Phase ◽  
Exponential Growth ◽  
Bacterial Species ◽  
Group B Streptococcus ◽  
Neonatal Meningitis ◽  
Exponential Growth Phase ◽  
Growth Phases ◽  
Group B

Serotype III group B Streptococcus (GBS) is the major cause of neonatal meningitis, but the risk of infection in the colonized neonates is variable. Capsular sialic acid (Sia), whose synthesis is encoded by neu genes, appears to be a major virulence factor in several bacterial species able to reach the cerebrospinal fluid. Therefore, variations of Sia expression related to the genetic diversity of strains may have an impact on the risk of meningitis in colonized neonates. We characterized by MLST the phylogenetic diversity of 64 serotype III GBS strains isolated from vaginal flora and randomly selected. These strains mostly belonged to three major sequence types (STs): ST1 (11 %), ST17 (39 %) and ST19 (31 %). The genetic diversity of strains of these lineages, characterized by PFGE, allowed the selection of 17 representative strains, three ST1, six ST17 and eight ST19, with NEM316 as reference, in order to evaluate (i) by quantitative RT-PCR, the level of transcription of the neuD gene as a marker for the transcription of neu genes and (ii) by enzymological analysis, the expression of Sia. The mean transcription level of neuD was higher for ST17 strains than for ST1 and ST19 strains in the early, mid- and late exponential growth phases, and was maximum in the early exponential growth phase for ST17 strains and in the mid-exponential growth phase for ST1 and ST19 strains. Mean Sia concentration was higher for ST17 than for ST1 and ST9 strains in all three growth phases. For the total population, Sia concentration varied notably in the stationary phase, from 0.38 to 9.30 nmol per 108 viable bacteria, with a median value of 2.99 nmol per 108 bacteria. All ST17 strains, only one-third of the ST19 strains and none of the ST1 strains had Sia concentrations higher than the median Sia concentration. Therefore, differences in the level of expression of Sia by strains of the major serotype III GBS phylogenetic lineages might be one of the factors that explain the leading role of ST17 strains in neonatal meningitis.

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