Structural Requirements for Glycosaminoglycan Recognition by the Lyme Disease Spirochete,
            <i>Borrelia burgdorferi</i>

Leong, John M.; Robbins, Douglas R.; Rosenfeld, Louis; Lahiri, Biswajit; Parveen, Nikhat

doi:10.1128/iai.66.12.6045-6048.1998

Cited by 39 publications

(34 citation statements)

References 25 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If Bgp promotes bacterial attachment to GAGs expressed on the surface of mammalian cells, exogenous Bgp should inhibit cell attachment. We previously showed that bacterial attachment to 293, Vero and C6 cells was mediated by GAGs (Leong et al, 1998b;Parveen et al, 1999). Therefore, we incubated monolayers of 293, Vero and C6 cells with recombinant Bgp (cleaved from GST-Bgp) prior to the addition of radiolabelled bacteria and Fig.…”

Section: Recombinant Bgp Inhibits Bacterial Attachment To Mammalian Cmentioning

confidence: 99%

“…Although a contribution of the core protein component of proteoglycans towards bacterial recognition in these experiments cannot be ruled out, current evidence suggests that polysaccharide moieties play the major role. For example, a relatively small segment of the GAG chain (16 residues) effectively inhibited bacterial attachment (Leong et al, 1998b). B. burgdorferi is also able to agglutinate trypsinized and fixed erythrocytes (Leong et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Haemagglutination has often been associated with lectin (sugar-binding) activity (Beeley, 1985) and Lyme disease strains that bind to GAGs demonstrate high haemagglutination activity (Leong et al, 1995). GAGs that inhibit cell attachment also inhibit haemagglutination and the ability of purified heparin fractions to inhibit cell attachment closely correlates with their ability to inhibit haemagglutination (Leong et al, 1998b). Given that heparin is not an efficient inhibitor of B. burgdorferi binding to the proteoglycan decorin and that the core protein of decorin plays an important role in recognition by B. burgdorferi (Guo et al, 1995), the GAG binding/haemagglutination and decorin binding activities of B. burgdorferi appear to be distinct.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi

Parveen

Leong

2000

Molecular Microbiology

Self Cite

142

146

View full text Add to dashboard Cite

Binding of glycosaminoglycans (GAGs) by Borrelia burgdorferi, the Lyme disease spirochete, has the potential to promote the colonization of diverse tissues. GAG binding by B. burgdorferi is associated with haemagglutination and we have identified a 26 kDa protein, which we have termed Bgp (BorreliaGAG‐binding protein), on the basis of its ability to bind to heparin and erythrocytes. Bgp was found in outer membrane fractions of B. burgdorferi and on the surface of intact bacteria, as assayed by labelling with a membrane‐impermeable biotinylating agent or anti‐Bgp antibodies. Purified recombinant Bgp agglutinated erythrocytes, binds to the same spectrum of GAGs as the B. burgdorferi strain from which the cloned bgp sequence was obtained, and inhibited B. burgdorferi binding to purified GAGs and to cultured mammalian cells. Thus, Bgp is a strong candidate for a GAG‐binding adhesin of B. burgdorferi.

show abstract

Section: Recombinant Bgp Inhibits Bacterial Attachment To Mammalian Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi

Parveen

Leong

2000

Molecular Microbiology

Self Cite

142

146

View full text Add to dashboard Cite

show abstract

“…The preferential localization in the loose connective tissue spaces between the collagen fiber bundles may reflect the well‐known binding affinity of the spirochetes to components of the extracellular matrix, especially proteoglycans(39–41). It is tempting to speculate that the low tissue turnover of collagenous connective tissue coupled with the paucity of immune effector cells may contribute to the persistence of Bb in this immunologically privileged site.…”

Section: Discussionmentioning

confidence: 99%

Insights from a novel three-dimensional in vitro model of Lyme arthritis: Standardized analysis of cellular and molecular interactions betweenBorrelia burgdorferi and synovial explants and fibroblasts

Franz

Fritze

Rittig

et al. 2001

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective To develop a novel 3‐dimensional (3‐D) in vitro model of Lyme arthritis to use in the study of the interactions between Borrelia burgdorferi (Bb) and human synovial host cells with respect to phagocytosis and potential persistence of Bb as well as the induction of proinflammatory cytokines and chemokines. Methods Two distinct culture systems, consisting of synovial membrane explants or interactive synovial cells embedded in 3‐D fibrin matrices, were chosen. Both systems were artificially infected with Bb, and the interactions between Bb and synovial tissue/cells were studied by histology, immunohistochemistry, and electron microscopy. Functional analyses included the induction/secretion of cytokines by Bb in the model system. Results Both culture systems proved to be stable and reproducible. The host cells and spirochetes showed high levels of viability and maintained their physiologic shape for >3 weeks. Bb invaded the synovial tissue and the artifical matrix in a time‐dependent manner. Host cells were activated by Bb, as indicated by the induction of interleukin‐1β and tumor necrosis factor α. Electron microscopic analysis revealed Bb intracellularly within macrophages as well as synovial fibroblasts, suggesting that not only professional phagocytes, but also resident synovial cells are capable of phagocytosing Bb. Most interestingly, the uptake of the spirochetes appeared to cause severe damage of the synovial fibroblasts, since the majority of these cells displayed ultrastructural features of disintegration. Conclusion A novel 3‐D in vitro model has been established that allows the study of distinct aspects of Lyme arthritis under conditions that resemble the pathologic condition in humans. This reproducible, standardized model supplements animal studies and conventional 2‐D cultures. The disintegration of synovial fibroblasts containing Bb or Bb fragments challenges the concept of an intracellular persistence of Bb and may instead reflect a mechanism that contributes to the inflammatory processes characteristic of Lyme arthritis.

show abstract

“…Site-directed mutagenesis of wildtype B subunit was carried out using standard kits and following the manufacturer's instructions. After mutagenesis of the TGT cysteine codon to the TCT serine codon the entire gene was sequenced and found to be otherwise identical to the published sequence [5].…”

Section: Bacteriamentioning

confidence: 99%

Formation of disulfide bonded dimer of mutated heat‐labile enterotoxin in vivo

Hedges

Hardy

1996

FEBS Letters

View full text Add to dashboard Cite

One of the two cysteines in the B subunit of heatlabile enterotoxin has been changed to a serine by site-directed mutagenesis so that the internal disulfide bond cannot form. The mutant protein, like the wild-type protein synthesised in the presence of the reducing agent dithiothreitol, does not form pentamers in the periplasm but binds to available membranes. Binding to membranes is disrupted by chaotropic agents but not by salt. More than half the molecules of mutant protein form disulfide-bonded dimers when exported to the periplasm but no dimer is detected when the protein is exported to the medium by spheroplasts.

show abstract

Structural Requirements for Glycosaminoglycan Recognition by the Lyme Disease Spirochete, Borrelia burgdorferi

Cited by 39 publications

References 25 publications

Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi

Identification of a candidate glycosaminoglycan‐binding adhesin of the Lyme disease spirochete Borrelia burgdorferi

Insights from a novel three-dimensional in vitro model of Lyme arthritis: Standardized analysis of cellular and molecular interactions betweenBorrelia burgdorferi and synovial explants and fibroblasts

Formation of disulfide bonded dimer of mutated heat‐labile enterotoxin in vivo

Contact Info

Product

Resources

About