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 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 767 TYPE 14 PNEUMOCOCCAL ANTISERA IS OPSONIC IN VITRO AND PROTECTIVE IN VIVO FOR GROUP B STREPTOCOCCUS TYPE III

1978 ◽  
Vol 12 ◽  
pp. 491-491 ◽  
Author(s):  
Gerald W Fischer ◽  
George H Lowell ◽  
Martin H Crumrine ◽  
James W Bass
Keyword(s):  
Group B Streptococcus ◽  
Type Iii ◽  
Group B

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 Glucuronoxylomannan, the Major Capsular Polysaccharide of Cryptococcus neoformans, Inhibits the Progression of Group B Streptococcal Arthritis

2004 ◽  
Vol 72 (11) ◽  
pp. 6367-6372 ◽  
Author(s):  
Luciana Tissi ◽  
Manuela Puliti ◽  
Francesco Bistoni ◽  
Paolo Mosci ◽  
Thomas R. Kozel ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cryptococcus Neoformans ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Peritoneal Macrophages ◽  
Type Iv ◽  
Inflammatory Protein ◽  
Group B

ABSTRACT Glucuronoxylomannan (GXM), the principal constituent of the Cryptococcus neoformans capsule, modulates the inflammatory response of human monocytes in vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound for use against experimental septic arthritis. Arthritis was induced in mice by the intravenous injection of 8 × 106 CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 μg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment markedly decreased the incidence and severity of articular lesions. Histological findings showed limited periarticular inflammation in the joints of GXM-treated mice, confirming the clinical observations. The amelioration of arthritis was associated with a significant reduction in the local production of interleukin-6 (IL-6), IL-1β, macrophage inflammatory protein 1α (MIP-1α), and MIP-2 and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS showed a similar pattern of cytokine production. The present study provides evidence for the modulation of the inflammatory response by GXM in vivo and suggests a potential therapeutic use for this compound in pathologies involving inflammatory processes.

scholarly journals Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK) Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Ozlem Equils ◽  
Chantelle Moffatt-Blue ◽  
Tomo-o Ishikawa ◽  
Charles F. Simmons ◽  
Vladimir Ilievski ◽  
...  
Keyword(s):  
Preterm Delivery ◽  
Group B Streptococcus ◽  
Pregnant Mouse ◽  
Tunel Staining ◽  
Pregnant Mice ◽  
Group B ◽  
Induced Apoptosis ◽  
In Vitro Treatment

Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis.Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery.Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection.Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery.Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

scholarly journals Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

2021 ◽  
Author(s):  
Marlyd E Mejia ◽  
Samantha Ottinger ◽  
Alison Vrbanac ◽  
Priyanka Babu ◽  
Jacob Zulk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Milk ◽  
Biofilm Formation ◽  
Group B Streptococcus ◽  
Human Milk Oligosaccharides ◽  
Vaginal Colonization ◽  
Vaginal Epithelial Cells ◽  
Group B

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.

scholarly journals Group B Streptococcus Pullulanase Crystal Structures in the Context of a Novel Strategy for Vaccine Development

2009 ◽  
Vol 191 (11) ◽  
pp. 3544-3552 ◽  
Author(s):  
Louise J. Gourlay ◽  
Isabella Santi ◽  
Alfredo Pezzicoli ◽  
Guido Grandi ◽  
Marco Soriani ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Vaccine Development ◽  
Group B Streptococcus ◽  
Carbohydrate Binding ◽  
Type I ◽  
Functional Studies ◽  
Group B ◽  
Anchoring Motif

ABSTRACT The group B streptococcus type I pullulanase (SAP) is a class 13 glycoside hydrolase that is anchored to the bacterial cell surface via a conserved C-terminal anchoring motif and involved in α-glucan degradation. Recent in vitro functional studies have shown that SAP is immunogenic in humans and that anti-SAP sera derived from immunized animals impair both group A and group B streptococcus pullulanase activities, suggesting that in vivo immunization with this antigen could prevent streptococcal colonization. To further investigate the putative role of SAP in bacterial pathogenesis, we carried out functional studies and found that recombinant SAP binds to human cervical epithelial cells. Furthermore, with a view of using SAP as a vaccine candidate, we present high-resolution crystal structure analyses of an N-terminally truncated form of SAP lacking the carbohydrate binding module but containing the catalytic domain and displaying glycosidase hydrolase activity, both in its apo form and in complex with maltotetraose, at resolutions of 2.1 and 2.4 Å, respectively.

Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

1993 ◽  
Vol 70 (04) ◽  
pp. 676-680 ◽  
Author(s):  
H F Kotzé ◽  
V van Wyk ◽  
P N Badenhorst ◽  
A du P Heyns ◽  
J P Roodt ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Life Span ◽  
Blood Platelets ◽  
Senescent Cell ◽  
Platelet Membrane ◽  
Antigen Complex ◽  
The Mean ◽  
Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

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