Attachment of Nontypable <i>Haemophilus influenzae</i> to Human Pharyngeal Epithelial Cells Mediated by a Ganglioside Receptor

Kawakami, Kenji; Ahmed, Kamruddin; Utsunomiya, Yoshiaki; Rikitomi, Naoto; Hori, Akihiro; Oishi, Kazunori; Nagatake, Tsuyoshi

doi:10.1111/j.1348-0421.1998.tb02342.x

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…13,15 However, the attachment inhibition method identified the receptors for both M. catarrhalis and H. influenzae. 16,17 Therefore, in this study the attachment inhibition method was used to detect the receptor for B. pseudomallei on pharyngeal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Gori¹,

Ahmed²,

Martinez³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Melioidosis is the term given to any infection caused by Burkholderia pseudomallei. This bacteria is one of the important causative agents of life-threatening pulmonary infections in the tropical and subtropical areas. The initiation of respiratory infections is attachment of this bacteria to pharyngeal cells. The precise mechanism of attachment of B. pseudomallei is not known. In this study, we found that asialoganglioside GM1 at concentrations of 25, 12.5, and 5 g/ml significantly decreased the attachment of B. pseudomallei strain Sp-186 in a dose-dependent manner. On the other hand, asialoganglioside GM2 decreased the attachment of B. pseudomallei, but only at a concentration of 25 g/ml. At a concentration of 1 mg/ml, glucose, N-acetyl-galactosamine, and galactose caused a significant decrease in attachment. However, at concentrations of 250 g/ml, no decrease in attachment was observed in B. pseudomallei treated with these carbohydrates. Mannose and fucose at concentrations of 1 mg/ml had no effects on the inhibition of attachment of B. pseudomallei. Four other isolates of B. pseudomallei showed a significant decrease in attachment after treatment with asialoganglioside GM1. We conclude that asialogangliosides GM1 and GM2 are part of the receptor complex for B. pseudomallei on human pharyngeal epithelial cells.Burkholderia pseudomallei can cause a variety of serious and life-threatening infections, collectively known as melioidosis. 1,2 High relapse, treatment failure, slow response to antibiotic treatment, and drug resistance have made this situation more difficult. 3-7 Septicemia and pulmonary infections are two main form of infection caused by B. pseudomallei. Kanaphun and others have shown that there is a relationship between pulmonary infection and pharyngeal colonization by this bacteria. 8 The initial step in the pathogenesis of respiratory infection is the attachment of bacteria to pharyngeal epithelial cells. The bacteria then enter the lower respiratory tract by microaspiration 9 and establish an infection by overcoming a series of body defense mechanisms. In a recent report, we have shown that B. pseudomallei has the capacity to attach to pharyngeal epithelial cells, and have developed a method for the in vitro study of the attachment of this bacteria to these cells. 10 Bacteria express adhesin, which mediates attachment to a specific receptor present on the host cell. It has been suggested that the receptor of B. pseudomallei on the pharyngeal epithelial cells is a polysaccharide. 10 Unraveling the mechanism of attachment will help in understanding the pathogenesis of this infection and aid in the development of prevention or treatment strategies based on the anti-attachment mechanism. Therefore, the present study was undertaken to identify the receptor for B. pseudomallei on human pharyngeal epithelial cells. MATERIALS AND METHODSBacteria. Five isolates of B. pseudomallei were used in this study. Three strains (Sp-186, Sp-335 and Sp-140) were isolated from sputum of patients with respir...

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Section: Discussionmentioning

confidence: 99%

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Gori¹,

Ahmed²,

Martinez³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Sialidase treatment of human pharyngeal epithelial cells inhibited adherence by H. influenzae (24). Peltola et al reported that mice infected with recombinant influenza viruses that carried higher neuraminidase (NA) activities were associated with a higher incidence of secondary pneumonia after inoculation with type 2 S. pneumoniae D39 strain.…”

Section: Vol 50 2006 Inhibition Of Influenza By Das181 1475mentioning

confidence: 99%

“…Cellular adhesion by some of the most important respiratory bacteria, including Haemophilus influenzae (10,24,55), Streptococcus pneumoniae (4), and Pseudomonas aeruginosa (3,16,28,39,40,43), have been reported to be mediated by binding to the sialic acid receptors on the host cells. Sialidase treatment of human pharyngeal epithelial cells inhibited adherence by H. influenzae (24).…”

Section: Vol 50 2006 Inhibition Of Influenza By Das181 1475mentioning

confidence: 99%

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Malakhov¹,

Aschenbrenner²,

Smee

et al. 2006

Antimicrob Agents Chemother

216

214

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Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes.

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“…[13] The role of GD2 in normal development is not well understood, though it is thought to play a role in neural differentiation and repair. [14] Gangliosides including GD2 may function as receptors for microbial toxins,[15] as well as mediators of cell adhesion. [16] In addition to its expression on breast cancer stem cells,[17] evidence for a tumorigenic role for GD2 includes its phosphorylation of tyrosine kinases,[18] enhancement of invasion and motility,[19] and immunosuppressive effect on effector cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-GD2 immunotherapy for neuroblastoma

Sait

Modak

2017

Expert Review of Anticancer Therapy

143

127

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Introduction: Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development. Expert commentary: Anti-GD2 monoclonal antibodies are associated with improved survival in patients in their first remission and are increasingly being used for chemorefractory and relapsed neuroblastoma. As protein engineering technology has become more accessible, newer antibody constructs are being tested. GD2 is also being targeted by natural killer cells and T-cells. Active immunity can be elicited by anti-GD2 vaccines. The rational combination of currently available and soon-to-emerge immunotherapeutic approaches, and their integration into conventional multimodality therapies will require further investigation to optimize their use for HR-NB.

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Attachment of Nontypable Haemophilus influenzae to Human Pharyngeal Epithelial Cells Mediated by a Ganglioside Receptor

Abstract: Abstract:Nontypable Haemophilus influenzae (NTHI)

Cited by 14 publications

References 23 publications

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Mediation of attachment of Burkholderia pseudomallei to human pharyngeal epithelial cells by the asialoganglioside GM1-GM2 receptor complex.

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Anti-GD2 immunotherapy for neuroblastoma

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