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Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease

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  • Authors: Beinan Wang1, P. Patrick Cleary2
  • Editors: Vincent A. Fischetti3, Richard P. Novick4, Joseph J. Ferretti5, Daniel A. Portnoy6, Miriam Braunstein7, Julian I. Rood8
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Institute of Microbiology, Chinese Academy of Sciences, Beijing China; 2: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN; 3: The Rockefeller University, New York, NY; 4: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 5: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 6: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 7: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 8: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec July 2019 vol. 7 no. 4 doi:10.1128/microbiolspec.GPP3-0049-2018
  • Received 29 November 2018 Accepted 03 December 2018 Published 05 July 2019
  • P. Patrick Cleary, [email protected]
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  • Abstract:

    The human oral-nasal mucosa is the primary reservoir for infections. Although the most common infection of consequence in temperate climates is pharyngitis, the past 25 years have witnessed a dramatic increase in invasive disease in many regions of the world. Historically, has been associated with sepsis and fulminate systemic infections, but the mechanism by which these streptococci traverse mucosal or epidermal barriers is not understood. The discovery that can be internalized by mammalian epithelial cells at high frequencies ( 1 3 ) and/or open tight junctions to pass between cells ( 4 ) provides potential explanations for changes in epidemiology and the ability of this species to breach such barriers. In this article, the invasins and pathways that uses to reach the intracellular state are reviewed, and the relationship between intracellular invasion and human disease is discussed.

  • Citation: Wang B, Cleary P. 2019. Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease. Microbiol Spectrum 7(4):GPP3-0049-2018. doi:10.1128/microbiolspec.GPP3-0049-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0049-2018
2019-07-05
2019-07-22

Abstract:

The human oral-nasal mucosa is the primary reservoir for infections. Although the most common infection of consequence in temperate climates is pharyngitis, the past 25 years have witnessed a dramatic increase in invasive disease in many regions of the world. Historically, has been associated with sepsis and fulminate systemic infections, but the mechanism by which these streptococci traverse mucosal or epidermal barriers is not understood. The discovery that can be internalized by mammalian epithelial cells at high frequencies ( 1 3 ) and/or open tight junctions to pass between cells ( 4 ) provides potential explanations for changes in epidemiology and the ability of this species to breach such barriers. In this article, the invasins and pathways that uses to reach the intracellular state are reviewed, and the relationship between intracellular invasion and human disease is discussed.

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Figures

Image of FIGURE 1
FIGURE 1

Scanning electron micrographs showing different stages of streptococci-HeLa cell interactions. A high density of microvilli surrounding and in contact with adherent streptococci. A common morphological change that microvilli undergo. The cup-like structure appears to gradually engulf the bacteria and ultimately pull them into a vacuole. A streptococcal chain has been partially ingested by a mechanism that morphologically resembles a receptor-ligand interaction. It is not known whether microvilli are involved in the latter or whether streptococci are ingested by two physically different cytoskeletal rearrangements.

Source: microbiolspec July 2019 vol. 7 no. 4 doi:10.1128/microbiolspec.GPP3-0049-2018
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Image of FIGURE 2
FIGURE 2

The various agonist and cellular receptors which streptococci commandeer to promote their own phagocytosis by epithelial cells. Both the M protein and high-affinity fibronectin proteins SfbI/PrtF1 are known invasins which depend on formation of a fibronectin bridge between the bacterial surface and integrin receptors α5β1 or αVβ3. Although less well studied, laminin can also serve as an agonist for ingestion of streptococci by linking them to α3β1 integrins. For some strains fibronectin-mediated invasion of epithelial cells also requires interaction between M protein and the complement regulatory protein CD46.

Source: microbiolspec July 2019 vol. 7 no. 4 doi:10.1128/microbiolspec.GPP3-0049-2018
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Image of FIGURE 3
FIGURE 3

Postulated and confirmed components of streptococci-induced focal adhesion complexes and signaling molecules required for formation of those complexes and subsequent cytoskeletal changes that lead to ingestion of streptococci by epithelial cells. Fibronectin (Fn) bound to surface M1 or SfbI/PrtF1 proteins associates with integrins to cause integrin clustering leading to ILK activation in a PI3K-dependent manner. For some strains contact between M protein and CD46 is also required for high-frequency invasion. The function of CD46 in this process, however, is unknown. Following recruitment of paxillin, FAK, and other focal adhesion proteins, autophosphorylation of FAK creates a docking site for Src kinases to phosphorylate recruited paxillin and additional sites on FAK. Alternatively, Rac and Cdc42 are activated by ILK through an intermediate to participate in formation of focal adhesion complexes, which provide an anchor for actin polymerization and cytoskeleton rearrangement that ultimately results in uptake of .

Source: microbiolspec July 2019 vol. 7 no. 4 doi:10.1128/microbiolspec.GPP3-0049-2018
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Image of FIGURE 4
FIGURE 4

IAV facilitates bacterial adherence through the activation of the TGF-β signaling pathway. IAV neuraminidase activates latent TGF-β, which launches Smad signals that locally upregulate integrin and Fn expression by infected cells, providing increased numbers of receptors for adherence of streptococci. This in turn could lead to increased susceptibility to more frequent and more serious streptococcal infections.

Source: microbiolspec July 2019 vol. 7 no. 4 doi:10.1128/microbiolspec.GPP3-0049-2018
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