Adsorption of Components of the Plasma Kinin-Forming System on the Surface ofPorphyromonas gingivalisInvolves Gingipains as the Major Docking Platforms

ABSTRACTEnhanced production of proinflammatory bradykinin-related peptides, the kinins, has been suggested to contribute to the pathogenesis of periodontitis, a common inflammatory disease of human gingival tissues. In this report, we describe a plausible mechanism of activation of the kinin-generating system, also known as the contact system or kininogen-kallikrein-kinin system, by the adsorption of its plasma-derived components such as high-molecular-mass kininogen (HK), prekallikrein (PK), and Hageman factor (FXII) to the cell surface of periodontal pathogenPorphyromonas gingivalis. The adsorption characteristics of mutant strains deficient in selected proteins of the cell envelope suggested that the surface-associated cysteine proteinases, gingipains, bearing hemagglutinin/adhesin domains (RgpA and Kgp) serve as the major platforms for HK and FXII adhesion. These interactions were confirmed by direct binding tests using microplate-immobilized gingipains and biotinylated contact factors. Other bacterial cell surface components such as fimbriae and lipopolysaccharide were also found to contribute to the binding of contact factors, particularly PK. Analysis of kinin release in plasma upon contact withP. gingivalisshowed that the bacterial surface-dependent mechanism is complementary to the previously described kinin generation system dependent on HK and PK proteolytic activation by the gingipains. We also found that severalP. gingivalisclinical isolates differed in the relative significance of these two mechanisms of kinin production. Taken together, these data show the importance of this specific type of bacterial surface-host homeostatic system interaction in periodontal infections.

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Nonulosonic acids contribute to the pathogenicity of the oral bacterium Tannerella forsythia

Interface Focus ◽

10.1098/rsfs.2018.0064 ◽

2019 ◽

Vol 9 (2) ◽

pp. 20180064 ◽

Cited By ~ 6

Author(s):

Susanne Bloch ◽

Markus B. Tomek ◽

Valentin Friedrich ◽

Paul Messner ◽

Christina Schäffer

Keyword(s):

Cell Surface ◽

Current Knowledge ◽

Cell Envelope ◽

Treatment Strategies ◽

Periodontal Pathogen ◽

Tannerella Forsythia ◽

Oral Bacterium ◽

Complex Protein ◽

Unique Cell ◽

Systemic Health

Periodontitis is a polymicrobial, biofilm-caused, inflammatory disease affecting the tooth-supporting tissues. It is not only the leading cause of tooth loss worldwide, but can also impact systemic health. The development of effective treatment strategies is hampered by the complicated disease pathogenesis which is best described by a polymicrobial synergy and dysbiosis model. This model classifies the Gram-negative anaerobe Tannerella forsythia as a periodontal pathogen, making it a prime candidate for interference with the disease. Tannerella forsythia employs a protein O -glycosylation system that enables high-density display of nonulosonic acids via the bacterium's two-dimensional crystalline cell surface layer. Nonulosonic acids are sialic acid-like sugars which are well known for their pivotal biological roles. This review summarizes the current knowledge of T. forsythia' s unique cell envelope with a focus on composition, biosynthesis and functional implications of the cell surface O -glycan. We have obtained evidence that glycobiology affects the bacterium's immunogenicity and capability to establish itself in the polymicrobial oral biofilm. Analysis of the genomes of different T. forsythia isolates revealed that complex protein O -glycosylation involving nonulosonic acids is a hallmark of pathogenic T. forsythia strains and, thus, constitutes a valuable target for the design of novel anti-infective strategies to combat periodontitis.

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Crystalline S-Layer Protein Monolayers Induce Water Turbulences on the Nanometer Scale

Crystals ◽

10.3390/cryst11091147 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1147

Author(s):

Rupert Tscheliessnig ◽

Andreas Breitwieser ◽

Uwe B. Sleytr ◽

Dietmar Pum

Keyword(s):

Cell Surface ◽

Molecular Sieves ◽

Cell Envelope ◽

Functional Model ◽

Ion Traps ◽

Coarse Grained ◽

Flow Profile ◽

Natural Habitats ◽

Bacterial Surface ◽

Wide Range

Bacterial surface layers (S-layers) have been observed as the outermost cell envelope component in a wide range of bacteria and most archaea. They are one of the most common prokaryotic cell surface structures and cover the cells completely. It is assumed that S-layers provide selection advantages to prokaryotic cells in their natural habitats since they act as protective envelopes, as structures involved in cell adhesion and surface recognition, as molecular or ion traps, and as molecular sieves in the ultrafiltration range. In order to contribute to the question of the function of S-layers for the cell, we merged high-resolution cryo-EM and small-angle X-ray scattering datasets to build a coarse-grained functional model of the S-layer protein SbpA from Lysinibacillus sphaericus ATCC 4525. We applied the Navier–Stokes and the Poisson equations for a 2D section through the pore region in the self-assembled SbpA lattice. We calculated the flow field of water, the vorticity, the electrostatic potential, and the electric field of the coarse-grained model. From calculated local changes in the flow profile, evidence is provided that both the characteristic rigidity of the S-layer and the charge distribution determine its rheological properties. The strength of turbulence and pressure near the S-layer surface in the range of 10 to 50 nm thus support our hypothesis that the S-layer, due to its highly ordered repetitive crystalline structure, not only increases the exchange rate of metabolites but is also responsible for the remarkable antifouling properties of the cell surface. In this context, studies on the structure, assembly and function of S-layer proteins are promising for various applications in nanobiotechnology, biomimetics, biomedicine, and molecular nanotechnology.

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Continuous, Topologically Guided Protein Crystallization Controls Bacterial Surface Layer Self-Assembly

10.1101/538397 ◽

2019 ◽

Cited By ~ 1

Author(s):

Colin J. Comerci ◽

Jonathan Herrmann ◽

Joshua Yoon ◽

Fatemeh Jabbarpour ◽

Xiaofeng Zhou ◽

...

Keyword(s):

Surface Layer ◽

Cell Surface ◽

Self Assembly ◽

Cell Envelope ◽

Protein Crystallization ◽

Bacterial Surface ◽

Cell Surface Structures ◽

Complicated Topology ◽

Layer Assembly

AbstractBacteria assemble the cell envelope using localized enzymes to account for growth and division of a topologically complicated surface1–3. However, a regulatory pathway has not been identified for assembly and maintenance of the surface layer (S-layer), a 2D crystalline protein coat surrounding the curved 3D surface of a variety of bacteria4,5. By specifically labeling, imaging, and tracking native and purified RsaA, the S-layer protein (SLP) fromC. crescentus, we show that protein self-assembly alone is sufficient to assemble and maintain the S-layerin vivo. By monitoring the location of newly produced S-layer on the surface of living bacteria, we find that S-layer assembly occurs independently of the site of RsaA secretion and that localized production of new cell wall surface area alone is insufficient to explain S-layer assembly patterns. When the cell surface is devoid of a pre-existing S-layer, the location of S-layer assembly depends on the nucleation characteristics of SLP crystals, which grow by capturing RsaA molecules freely diffusing on the outer bacterial surface. Based on these observations, we propose a model of S-layer assembly whereby RsaA monomers are secreted randomly and diffuse on the lipopolysaccharide (LPS) outer membrane until incorporated into growing 2D S-layer crystals. The complicated topology of the cell surface enables formation of defects, gaps, and grain boundaries within the S-layer lattice, thereby guiding the location of S-layer assembly without enzymatic assistance. This unsupervised mechanism poses unique challenges and advantages for designing treatments targeting cell surface structures or utilizing S-layers as self-assembling macromolecular nanomaterials. As an evolutionary driver, 2D protein self-assembly rationalizes the exceptional S-layer subunit sequence and species diversity6.

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Myeloperoxidase Interacts with Endothelial Cell-Surface Cytokeratin 1 and Modulates Bradykinin Production by the Plasma Kallikrein-Kinin System

American Journal Of Pathology ◽

10.2353/ajpath.2007.060831 ◽

2007 ◽

Vol 171 (1) ◽

pp. 349-360 ◽

Cited By ~ 34

Author(s):

Joshua M. Astern‡ ◽

William F. Pendergraft ◽

Ronald J. Falk‡ ◽

J. Charles Jennette‡ ◽

Alvin H. Schmaier ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Surface ◽

Plasma Kallikrein ◽

Kinin System ◽

Endothelial Cell Surface ◽

Kallikrein Kinin System

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Involvement of kallikrein-kinin system in development of experimental ulcerative colitis induced by dextran sulfate sodium in rats

Gastroenterology ◽

10.1016/s0016-5085(01)83453-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A694-A694

Author(s):

K KAMATA ◽

I HAYASHI ◽

K BOKU ◽

T SAEKI ◽

T OHNO ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Kinin System ◽

Kallikrein Kinin System ◽

Experimental Ulcerative Colitis

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Abstract #787706: Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy

Endocrine Practice ◽

10.1016/s1530-891x(20)39428-3 ◽

2020 ◽

Vol 26 ◽

pp. 88-89

Author(s):

Hyun Kyung Kim

Keyword(s):

Diabetic Retinopathy ◽

Neutrophil Extracellular Trap ◽

Factor Xii ◽

Kinin System ◽

Trap Formation ◽

Extracellular Trap ◽

Kallikrein Kinin System

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Einfluss mechanischer Dehnung von alveolären Typ II Zellen auf das Kallikrein-Kinin System

Pneumologie ◽

10.1055/s-0036-1572298 ◽

2016 ◽

Vol 70 (S 01) ◽

Author(s):

J Knauth ◽

A Schweinberger ◽

H Kuhn ◽

H Wirtz

Keyword(s):

Kinin System ◽

Kallikrein Kinin System

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Mechanisms of Signaling through Urokinase Receptor and the Cellular Response

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615847 ◽

1999 ◽

Vol 82 (08) ◽

pp. 305-311 ◽

Cited By ~ 31

Author(s):

Yuri Koshelnick ◽

Monika Ehart ◽

Hannes Stockinger ◽

Bernd Binder

Keyword(s):

Cell Surface ◽

Proteolytic Activity ◽

Tumor Invasion ◽

Cellular Response ◽

Transmembrane Protein ◽

Urokinase Receptor ◽

Biological Processes ◽

In Vivo Models ◽

Proteolytic Activation ◽

Core Proteins

IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in a number of biological processes, including local fibrinolysis, tumor invasion, angiogenesis, neointima and atherosclerotic plaque formation, inflammation, and matrix remodeling during wound healing and development.1-6 Binding of urokinase to its specific receptor provides cells with a localized proteolytic potential. It stimulates conversion of cell surface-bound plasminogen into active plasmin, which, in turn, is required for proteolytic degradation of basement membrane components, including fibronectin, collagen, laminin, and proteoglycan core proteins.7 Moreover, plasmin activates other matrix-degrading enzymes, such as matrix metalloproteinases.8 Overexpression of u-PA/u-PAR correlates with tumor invasion and metastasis formation,9-13 while reduction of cell-surface bound u-PA and inhibition of u-PAR expression leads to a significant decrease of invasive and metastatic activity.14 Specific antagonists that suppress binding of u-PA to u-PAR have been shown to inhibit cell-surface plasminogen activation, tumor growth, and angiogenesis both in vitro and in vivo models.15,16 Independently of its proteolytic activity, u-PA is implicated in many biological processes that seem to require u-PAR-mediated intracellular signal transduction, such as proliferation, chemotactic movement and adhesion, migration, and differentiation.17 Data obtained in the late 1980s indicated that u-PA not only provides cells with local proteolytic activity, but might also be capable of transducing signals to the cell.18-22 At that time, however, the u-PAR has just been isolated, cloned, and identified as a glycosylphosphatidylinositol (GPI)-linked protein and not a transmembrane protein. Signaling via the u-PAR was, therefore, regarded as being unlikely, and the effects of u-PA on cell proliferation18-22 were thought to be mediated by proteolytic activation of latent growth factors. The assumption of direct signaling via u-PAR was, in fact, considered controversial, until about 10 years later when a physical association between u-PAR and signaling proteins was found.23 From this report on, several proteins associated with u-PAR have been identified. Now, u-PAR seems to be part of a large “signalosome” associated and interacting with several proteins on both the outside and inside of the cell.

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