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Extracellular Matrix Interactions with Gram-Positive Pathogens

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  • Authors: Sven Hammerschmidt1, Manfred Rohde2, Klaus T. Preissner3
  • Editors: Vincent A. Fischetti4, Richard P. Novick5, Joseph J. Ferretti6, Daniel A. Portnoy7, Miriam Braunstein8, Julian I. Rood9
    Affiliations: 1: Department of Molecular Genetics and Infection Biology, Center for Functional Genomics of Microbes, University of Greifswald, D-17487 Greifswald, Germany; 2: Central Facility for Microscopy, Helmholtz-Center for Infection Research, D-38124 Braunschweig, Germany; 3: Institute for Biochemistry, Medical School, Justus-Liebig-University, D-35392 Giessen, Germany; 4: The Rockefeller University, New York, NY; 5: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 6: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 7: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 8: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 9: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0041-2018
  • Received 16 August 2018 Accepted 14 March 2019 Published 19 April 2019
  • Klaus T. Preissner, [email protected]
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  • Abstract:

    The main strategies used by pathogenic bacteria to infect eukaryotic tissue include their adherence to cells and the extracellular matrix (ECM), the subsequent colonization and invasion as well as the evasion of immune defences. A variety of structurally and functionally characterized adhesins and binding proteins of gram-positive bacteria facilitate these processes by specifically recognizing and interacting with various components of the host ECM, including different collagens, fibronectin and other macromolecules. The ECM affects the cellular physiology of our body and is critical for adhesion, migration, proliferation, and differentiation of many host cell types, but also provides the support for infiltrating pathogens, particularly under conditions of injury and trauma. Moreover, microbial binding to a variety of adhesive components in host tissue fluids leads to structural and/or functional alterations of host proteins and to the activation of cellular mechanisms that influence tissue and cell invasion of pathogens. Since the diverse interactions of gram-positive bacteria with the ECM represent important pathogenicity mechanisms, their characterization not only allows a better understanding of microbial invasion but also provides clues for the design of novel therapeutic strategies to manage infectious diseases.

  • Citation: Hammerschmidt S, Rohde M, Preissner K. 2019. Extracellular Matrix Interactions with Gram-Positive Pathogens. Microbiol Spectrum 7(2):GPP3-0041-2018. doi:10.1128/microbiolspec.GPP3-0041-2018.


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The main strategies used by pathogenic bacteria to infect eukaryotic tissue include their adherence to cells and the extracellular matrix (ECM), the subsequent colonization and invasion as well as the evasion of immune defences. A variety of structurally and functionally characterized adhesins and binding proteins of gram-positive bacteria facilitate these processes by specifically recognizing and interacting with various components of the host ECM, including different collagens, fibronectin and other macromolecules. The ECM affects the cellular physiology of our body and is critical for adhesion, migration, proliferation, and differentiation of many host cell types, but also provides the support for infiltrating pathogens, particularly under conditions of injury and trauma. Moreover, microbial binding to a variety of adhesive components in host tissue fluids leads to structural and/or functional alterations of host proteins and to the activation of cellular mechanisms that influence tissue and cell invasion of pathogens. Since the diverse interactions of gram-positive bacteria with the ECM represent important pathogenicity mechanisms, their characterization not only allows a better understanding of microbial invasion but also provides clues for the design of novel therapeutic strategies to manage infectious diseases.

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Image of FIGURE 1

Adhesion of SfbI (streptococcal fibronectin binding protein I)-expressing GAS to an epithelial cell (HEp-2) mediated by fibronectin, which serves as a bridging molecule between streptococci and host cell integrins. Invasion of SfbI-expressing streptococci (red) into an epithelial cell through the formation of invaginations by coopting host cell caveolae, fibronectin, and integrins. expressing SfbI protein without exposure to fibronectin; this serves as a control to expressing SfbI after incubation with fibronectin and subsequent labeling with antifibronectin antibodies and protein A gold-nanoparticles; note the strong binding of fibronectin to the surface of the bacteria via SfbI protein (white gold-nanoparticle dots). Invasion of non-SfbI-expressing streptococci (red) into an epithelial cell (HEp-2) through signal induction of membrane ruffling of the host cell. expressing SfbI on its surface after incubation with type IV collagen alone; note the smooth bacterial surface. Preincubation of SfbI-expressing with fibronectin, followed by exposure to type IV collagen, results in a drastic accumulation of collagen on the bacterial surface. Detection of type IV collagen on the surface of SfbI-expressing , following incubation with fibronectin and collagen IV (white gold-nanoparticle dots). Direct binding of M3 serotype streptococci (red) to mouse type I collagen (derived from the mouse tail). Bars represent 1 μm in panels A, B, and E to I and 0.5 μm in panels C and D.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0041-2018
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Image of FIGURE 2

( to ) Dissolution of a fibrin clot by (D39, serotype 2). fibrin clot after fixation with aldehydes, dehydration with acetone, and critical-point drying that was subsequently exposed to in the presence of host-derived plasminogen activator and plasminogen; no dissolution of the fixed fibrin clot. Following binding of plasminogen to its bacterial binding protein α-enolase and addition of plasminogen activator and plasminogen, the formed plasmin degrades native fibrin bundles. Higher magnification of the process shown in panel B to demonstrate the dissolution of thick fibrin bundles (compare with panel D). The same process as shown in panel C, except that a plasmin inhibitor was added to prevent the degradation of fibrin bundles. Adhesion and initial invasion of (serotype 35A) to a Detroit 562 human nasopharyngeal carcinoma cell, mediated by bacterial binding of vitronectin and its interaction with host cell integrins, inducing a signaling cascade via integrin-linked kinase. Two invasion mechanisms of methicillin-resistant into epithelial cells (HeLa): via the formation of large invaginations and by inducing rearrangements of the actin cytoskeleton of the host cell, i.e., membrane ruffling. Bars represent 10 μm in panel A, 200 μm in panel B, and 1 μm in panels C to G.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0041-2018
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surface proteins that recognize ECM molecules, plasminogen, and C4b-binding protein (C4bBP)

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0041-2018
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surface proteins that recognize ECM molecules

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0041-2018

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