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 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 Lipophilic Dye Staining of Cryptococcus neoformans Extracellular Vesicles and Capsule

2009 ◽  
Vol 8 (9) ◽  
pp. 1373-1380 ◽  
Author(s):  
André Moraes Nicola ◽  
Susana Frases ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Extracellular Vesicles ◽  
Capsular Polysaccharide ◽  
Complex Structure ◽  
Spectral Characteristics ◽  
Acid Dyes ◽  
Whole Cells ◽  
Direct Binding

ABSTRACT Cryptococcus neoformans is an encapsulated yeast that causes systemic mycosis in immunosuppressed individuals. Recent studies have determined that this fungus produces vesicles that are released to the extracellular environment both in vivo and in vitro. These vesicles contain assorted cargo that includes several molecules associated with virulence and implicated in host-pathogen interactions, such as capsular polysaccharides, laccase, urease, and other proteins. To date, visualization of extracellular vesicles has relied on transmission electron microscopy, a time-consuming technique. In this work we report the use of fluorescent membrane tracers to stain lipophilic structures in cryptococcal culture supernatants and capsules. Two dialkylcarbocyanine probes with different spectral characteristics were used to visualize purified vesicles by fluorescence microscopy and flow cytometry. Dual staining of vesicles with dialkylcarbocyanine and RNA-selective nucleic acid dyes suggested that a fraction of the vesicle population carried RNA. Use of these dyes to stain whole cells, however, was hampered by their possible direct binding to capsular polysaccharide. A fluorescent phospholipid was used as additional membrane tracer to stain whole cells, revealing punctate structures on the edge of the capsule which are consistent with vesicular trafficking. Lipophilic dyes provide new tools for the study of fungal extracellular vesicles and their content. The finding of hydrophobic regions in the capsule of C. neoformans adds to the growing evidence for a structurally complex structure composed of polysaccharide and nonpolysaccharide components.

scholarly journals Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yiyi Jin ◽  
Jianchang Qian ◽  
Xin Ju ◽  
Xiaodong Bao ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

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 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 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.

Antibodies to the capsular polysaccharide of Neisseria meningitidis group B or E. coli K1 bind to the brains of infant rats in vitro but not in vivo

1986 ◽  
Vol 1 (1) ◽  
pp. 101-105 ◽  
Author(s):  
Kirsi Saukkonen ◽  
Matti Haltia ◽  
Matthias Frosch ◽  
Dieter Bitter-Süerman ◽  
Maija Leinonen
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
E Coli ◽  
Infant Rats ◽  
Group B

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.

Sign in / Sign up

Export Citation Format

Share Document