scholarly journals Role of sialidase in glycoprotein utilization by Tannerella forsythia

Microbiology ◽  
2011 ◽  
Vol 157 (11) ◽  
pp. 3195-3202 ◽  
Author(s):  
Sumita Roy ◽  
Kiyonobu Honma ◽  
C. W. Ian Douglas ◽  
Ashu Sharma ◽  
Graham P. Stafford
Keyword(s):  
Sialic Acid ◽  
Tannerella Forsythia ◽  
Similar Reduction ◽  
Biofilm Growth ◽  
Sialidase Activity ◽  
Sialidase Inhibitor ◽  
Initial Adhesion ◽  
Coated Surfaces

The major bacterial pathogens associated with periodontitis include Tannerella forsythia. We previously discovered that sialic acid stimulates biofilm growth of T. forsythia, and that sialidase activity is key to utilization of sialoconjugate sugars and is involved in host–pathogen interactions in vitro. The aim of this work was to assess the influence of the NanH sialidase on initial biofilm adhesion and growth in experiments where the only source of sialic acid was sialoglycoproteins or human oral secretions. After showing that T. forsythia can utilize sialoglycoproteins for biofilm growth, we showed that growth and initial adhesion with sialylated mucin and fetuin were inhibited two- to threefold by the sialidase inhibitor oseltamivir. A similar reduction (three- to fourfold) was observed with a nanH mutant compared with the wild-type. Importantly, these data were replicated using clinically relevant serum and saliva samples as substrates. In addition, the ability of the nanH mutant to form biofilms on glycoprotein-coated surfaces could be restored by the addition of purified NanH, which we show is able to cleave sialic acid from the model glycoprotein fetuin and, much less efficiently, 9-O-acetylated bovine submaxillary mucin. These data show for the first time that glycoprotein-associated sialic acid is likely to be a key in vivo nutrient source for T. forsythia when growing in a biofilm, and suggest that sialidase inhibitors might be useful adjuncts in periodontal therapy.

scholarly journals The NEU1-selective sialidase inhibitor, C9-butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo

Glycobiology ◽  
2016 ◽  
Vol 26 (8) ◽  
pp. 834-849 ◽  
Author(s):  
Sang W Hyun ◽  
Anguo Liu ◽  
Zhenguo Liu ◽  
Alan S Cross ◽  
Avelino C Verceles ◽  
...  
Keyword(s):  
Human Lung ◽  
Murine Lung ◽  
Sialidase Activity ◽  
Sialidase Inhibitor

Sialic Acid Loss Regulates Platelet Survival and Integrity

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3504-3504
Author(s):  
Renata Grozovsky ◽  
Gerard Jansen ◽  
Karin M. Hoffmeister
Keyword(s):  
Flow Cytometry ◽  
Sialic Acid ◽  
Conflicts Of Interest ◽  
Surface Expression ◽  
Sialidase Activity ◽  
Acetylneuraminic Acid ◽  
Platelet Survival ◽  
Sialidase Inhibitor ◽  
Glycan Degradation

Abstract It becomes increasingly apparent that, besides the intrinsic apoptotic machinery, surface glycan modifications regulate platelet survival. Platelets with reduced α2,3-linked sialic acid during sepsis due to S. pneumoniae infection, after cold storage, or in mice lacking the sialyltransferase ST3GalIV are cleared by the hepatic Ashwell-Morell receptor (AMR, ASGPR1/2). Platelet survival in Asgr2-/- mice was increased by ∼35% when compared to that of WT mice, which results in a ∼50% increase in circulating platelet counts, despite a loss of surface sialic acid. We reasoned that sialidase activity increases on the surface of circulating platelets as they age, a process that would facilitate sialic acid hydrolysis and removal from the circulation. To test this hypothesis, we directly injected the sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA) into WT mice and determined endogenous platelet circulatory times. Platelet survival was prolonged by ∼30% (T1/2 of 62.0 ± 2.7 h) in DANA-treated mice, compared to that of mock-treated mice (T1/2 of 47.5 ± 4.3 h). DANA injections decreased terminal sialic acid loss on circulating platelets by ∼40% by day 2, compared to control platelets, as evidenced by binding of RCA-I lectin that specifically recognizes terminal β1-4 galactose moieties exposed by sialic acid removal. Freshly isolated, resting platelets from Asgr2-/- mice (AMR-platelets) were significantly smaller in size (22%) and had increased sialidase Neu1 (∼5 fold), but not Neu3 surface expression, when compared to WT platelets or St3gal4-/- platelets, as measured by flow cytometry. We next investigated if AMR-platelets age/deteriorate faster upon in vitro storage. Platelets were isolated from WT, Asgr2-/- and St3gal4-/- mice and stored for 24hrs at room temperature, and sialidase expression (Neu1 and Neu3) as well as microvesiculation were measured by flow cytometry. Although significant Neu1 and Neu3 surface expression increase was measured on platelets from all phenotype after storage, Neu1 and Neu3 surface expression was significantly higher in AMR-platelets (∼2 and 4 fold, respectively) when compared to WT and St3gal4-/- platelets. AMR-platelets, but not St3gal4-/- platelets microvesiculated upon storage, consistent with a faster deterioration of aged AMR-platelets. We next injected into WT and Asgr2-/- mice the BH3 mimetic, ABT-737, which binds and inhibits the pro-apoptotic Bcl-2, Bcl-xL and Bcl-w. After injection of ABT-737, platelets in the Asgr2-/- mouse were cleared more efficiently (∼20%) from the circulation when compared to those in WT mice. Collectively, our data show that blood borne sialidases contribute to loss of sialic acid during circulation to regulate platelet survival. Our data also suggest that platelet glycan degradation, i.e. sialic acid loss, may trigger the intrinsic apoptotic machinery in platelets, linking glycan degradation and intrinsic apoptotic machinery in the clearance mechanisms regulating platelet survival. Disclosures: No relevant conflicts of interest to declare.

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.

In vitro study of monocyte viability during the initial adhesion to albumin- and fibrinogen-coated surfaces

Biomaterials ◽  
2001 ◽  
Vol 22 (8) ◽  
pp. 827-832 ◽  
Author(s):  
M. Werthén ◽  
A. Sellborn ◽  
M. Källtorp ◽  
H. Elwing ◽  
P. Thomsen
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Initial Adhesion ◽  
Coated Surfaces

scholarly journals Relevance of Biofilm Models in Periodontal Research: From Static to Dynamic Systems

2021 ◽  
Vol 9 (2) ◽  
pp. 428
Author(s):  
María Carmen Sánchez ◽  
Andrea Alonso-Español ◽  
Honorato Ribeiro-Vidal ◽  
Bettina Alonso ◽  
David Herrera ◽  
...  
Keyword(s):  
Research Group ◽  
Surface Composition ◽  
Bacterial Colonization ◽  
Implant Surface ◽  
Biofilm Growth ◽  
Biofilm Model ◽  
Dental Implant Surface ◽  
The Impact

Microbial biofilm modeling has improved in sophistication and scope, although only a limited number of standardized protocols are available. This review presents an example of a biofilm model, along with its evolution and application in studying periodontal and peri-implant diseases. In 2011, the ETEP (Etiology and Therapy of Periodontal and Peri-Implant Diseases) research group at the University Complutense of Madrid developed an in vitro biofilm static model using representative bacteria from the subgingival microbiota, demonstrating a pattern of bacterial colonization and maturation similar to in vivo subgingival biofilms. When the model and its methodology were standardized, the ETEP research group employed the validated in vitro biofilm model for testing in different applications. The evolution of this model is described in this manuscript, from the mere observation of biofilm growth and maturation on static models on hydroxyapatite or titanium discs, to the evaluation of the impact of dental implant surface composition and micro-structure using the dynamic biofilm model. This evolution was based on reproducing the ideal microenvironmental conditions for bacterial growth within a bioreactor and reaching the target surfaces using the fluid dynamics mimicking the salivary flow. The development of this relevant biofilm model has become a powerful tool to study the essential processes that regulate the formation and maturation of these important microbial communities, as well as their behavior when exposed to different antimicrobial compounds.

scholarly journals Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation.

1983 ◽  
Vol 157 (1) ◽  
pp. 371-376 ◽  
Author(s):  
M Fogel ◽  
P Altevogt ◽  
V Schirrmacher
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Tumor Cell ◽  
Metastatic Potential ◽  
Lectin Receptors ◽  
Lectin Receptor ◽  
Receptor Sites ◽  
Variant Line

A plastic adherent variant line (ESb-M) of a highly invasive and metastatic murine T cell lymphoma (ESb) was found to have lost its metastatic potential while still being tumorigenic in normal syngeneic hosts. The variant retained most of its ESb-derived antigenic and biochemical characteristics but differed at binding sites for certain lectins with specificity for terminal N-acetylgalactosamine residues. Whereas such sites were masked by sialic acid on metastatic ESb cells, they became unmasked on the adherent variant line. Metastatic revertants of ESb-M cells did not express the respective lectin receptor sites because these were again masked by sialic acid. It is suggested that the masking of specific lectin receptors sites on the tumor cell surface is of crucial importance for metastatis. If freely exposed, these sites may change adherence characteristics of the cells possibly not only in vitro (to plastic) but also in vivo.

scholarly journals Role of Sialic Acid and Complex Carbohydrate Biosynthesis in Biofilm Formation by Nontypeable Haemophilus influenzae in the Chinchilla Middle Ear

2005 ◽  
Vol 73 (6) ◽  
pp. 3210-3218 ◽  
Author(s):  
Joseph Jurcisek ◽  
Laura Greiner ◽  
Hiroshi Watanabe ◽  
Anthony Zaleski ◽  
Michael A. Apicella ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Haemophilus Influenzae ◽  
Middle Ear ◽  
Biofilm Formation ◽  
Mammalian Host ◽  
Nontypeable Haemophilus Influenzae ◽  
Biofilm Production ◽  
Tract Infections

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) is an important pathogen in respiratory tract infections, including otitis media (OM). NTHI forms biofilms in vitro as well as in the chinchilla middle ear, suggesting that biofilm formation in vivo might play an important role in the pathogenesis and chronicity of OM. We've previously shown that SiaA, SiaB, and WecA are involved in biofilm production by NTHI in vitro. To investigate whether these gene products were also involved in biofilm production in vivo, NTHI strain 2019 and five isogenic mutants with deletions in genes involved in carbohydrate biosynthesis were inoculated into the middle ears of chinchillas. The wild-type strain formed a large, well-organized, and viable biofilm; however, the wecA, lsgB, siaA, pgm, and siaB mutants were either unable to form biofilms or formed biofilms of markedly reduced mass, organization, and viability. Despite their compromised ability to form a biofilm in vivo, wecA, lsgB, and siaA mutants survived in the chinchilla, inducing culture-positive middle ear effusions, whereas pgm and siaB mutants were extremely sensitive to the bactericidal activity of chinchilla serum and thus did not survive. Lectin analysis indicated that sialic acid was an important component of the NTHI 2019 biofilm produced in vivo. Our data suggested that genes involved in carbohydrate biosynthesis and assembly play an important role in the ability of NTHI to form a biofilm in vivo. Collectively, we found that when modeled in a mammalian host, whereas biofilm formation was not essential for survivability of NTHI in vivo, lipooligosaccharide sialylation was indispensable.

scholarly journals Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190653 ◽  
Author(s):  
Takeo Tatsuta ◽  
Toshiyuki Satoh ◽  
Shigeki Sugawara ◽  
Akiyoshi Hara ◽  
Masahiro Hosono
Keyword(s):  
Sialic Acid ◽  
Cell Growth ◽  
Malignant Mesothelioma ◽  
Sialic Acid Binding ◽  
Mesothelioma Cell ◽  
Binding Lectin

Inhibition of Casein Kinase 2 Impairs Wnt Signaling and Cell Survival in Chronic Lymphocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2050-2050
Author(s):  
Christina Wu ◽  
Fitzgerald S Lao ◽  
Emily Nan ◽  
Hongying Li ◽  
Michael Y. Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Conflicts Of Interest ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Lymphocytic Leukemia ◽  
Similar Reduction ◽  
Gene Assay

Abstract The oncogenic Wnt pathway is aberrantly activated in most CLL clones, and hence is an attractive target for therapy. The casein kinase 2 (CK2) enzyme is an established positive regulator of Wnt signaling. The inhibitor Silmitasertib, also known as CX-4945, is a nanomolar inhibitor of CK2. It has been reported that CK2 is overexpressed in CLL. Here we have investigated the effects of CX-4945 on WNT signaling in primary CLL cells. We confirmed that CX-4945 displayed in vitro cytotoxic activity toward CLL cells at very low µM concentration, as previously reported by others. However, at least 2-3 fold higher concentration of CX-4945 was required to achieve a similar toxicity against normal PBMC. Previously, our laboratory has successfully utilized a short-term CLL "parking" model in immunodeficient RAG/gamma chain knock out (RG-KO) mice to evaluate the in vivo efficacy and potential toxicity of anti-CLL agents. CX-4945 at dosages of 0.3-10 mg/kg was administered by oral gavage daily for 6 days to mice injected i.p. with 10 million CLL cells. These dosages of drug were well tolerated, and potently inhibited CLL persistence in the xenotransplanted mice. In a reporter gene assay, CX-4945 dose-dependently inhibited Wnt target gene expression. Furthermore, inhibition of dishevelled-2 (Dvl-2) protein expression was observed in primary CLL patient samples treated with 3-10 µM CX-4945 for 4-16 hours. Similar reduction in p-GSK3b(S9) protein was also observed. Quantitative RT-PCR also confirmed down regulation of b-catenin gene expression in primary CLL patient samples treated with 10 µM CX-4945 for 4h. Further molecular analyses of predictive or correlative biomarkers is ongoing using Nanostring PanCancer multipathway gene analysis. In a preliminary study, we found that CX-4945 perturbed the expression of multiple genes implicated in CLL development and survival. In summary, the CK2 inhibitor CX-4945 inhibited Wnt signaling and CLL survival, and displayed oral activity in mice. CK2 inhibitors are thus potential therapeutic agents for CLL. Disclosures No relevant conflicts of interest to declare.

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