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Capsular Polysaccharide of Group A

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  • Author: Michael R. Wessels1
  • Editors: Vincent A. Fischetti2, Richard P. Novick3, Joseph J. Ferretti4, Daniel A. Portnoy5, Miriam Braunstein6, Julian I. Rood7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, MA; 2: The Rockefeller University, New York, NY; 3: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 4: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 5: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 6: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 7: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018
  • Received 29 November 2018 Accepted 10 December 2018 Published 11 January 2019
  • Michael R. Wessels, [email protected]
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  • Abstract:

    Most clinical isolates of elaborate a capsular polysaccharide, which is composed of hyaluronic acid, a high-molecular-mass polymer of alternating residues of -acetyl glucosamine and glucuronic acid. Certain strains, particularly those of the M18 serotype, produce abundant amounts of capsule, resulting in formation of large, wet-appearing, translucent or “mucoid” colonies on solid media, whereas strains of M-types 4 and 22 produce none. Studies of acapsular mutant strains have provided evidence that the capsule enhances virulence in animal models of infection, an effect attributable, at least in part, to resistance to complement-mediated opsonophagocytic killing by leukocytes. The presence of the hyaluronic acid capsule may mask adhesins on the bacterial cell wall. However, the capsule itself can mediate bacterial attachment to host cells by binding to the hyaluronic-acid binding protein, CD44. Furthermore, binding of the capsule to CD44 on host epithelial cells can trigger signaling events that disrupt cell-cell junctions and facilitate bacterial invasion into deep tissues. This article summarizes the biochemistry, genetics, regulation, and role in pathogenesis of this important virulence determinant.

  • Citation: Wessels M. 2019. Capsular Polysaccharide of Group A . Microbiol Spectrum 7(1):GPP3-0050-2018. doi:10.1128/microbiolspec.GPP3-0050-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0050-2018
2019-01-11
2019-10-23

Abstract:

Most clinical isolates of elaborate a capsular polysaccharide, which is composed of hyaluronic acid, a high-molecular-mass polymer of alternating residues of -acetyl glucosamine and glucuronic acid. Certain strains, particularly those of the M18 serotype, produce abundant amounts of capsule, resulting in formation of large, wet-appearing, translucent or “mucoid” colonies on solid media, whereas strains of M-types 4 and 22 produce none. Studies of acapsular mutant strains have provided evidence that the capsule enhances virulence in animal models of infection, an effect attributable, at least in part, to resistance to complement-mediated opsonophagocytic killing by leukocytes. The presence of the hyaluronic acid capsule may mask adhesins on the bacterial cell wall. However, the capsule itself can mediate bacterial attachment to host cells by binding to the hyaluronic-acid binding protein, CD44. Furthermore, binding of the capsule to CD44 on host epithelial cells can trigger signaling events that disrupt cell-cell junctions and facilitate bacterial invasion into deep tissues. This article summarizes the biochemistry, genetics, regulation, and role in pathogenesis of this important virulence determinant.

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Figures

Image of FIGURE 1
FIGURE 1

Schematic diagram of the operon and the function of each gene product in the biosynthetic pathway for synthesis of hyaluronic acid in .

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018
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Image of FIGURE 2
FIGURE 2

Map of the region of the chromosome that includes the operon encoding enzymes required for hyaluronic acid synthesis. The other genes shown appear not to be involved in capsular polysaccharide synthesis or surface expression. In some strains insertion sequence IS′ is present approximately 50 nucleotides upstream of the operon promoter (adapted from the genome sequence of M1 strain SF370, GenBank accession number AE004092 [ 93 ]).

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018
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Image of FIGURE 3
FIGURE 3

Diagram of the chromosomal locus encoding a two-component regulatory system that regulates hyaluronic acid synthesis. Sequences corresponding to regions of the predicted proteins with properties characteristic of the response regulator (CsrR) or sensor (CsrS) components are indicated (adapted from the genome sequence of M3 strain MGAS315, GenBank accession number AE014074 [ 94 ]).

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018
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Image of FIGURE 4
FIGURE 4

The hyaluronic acid capsule and resistance to complement-mediated phagocytosis. The capsule does not prevent deposition of C3b on the bacterial cell wall but, rather, interferes with the interaction of bound C3b with phagocyte receptors.

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018
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Tables

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TABLE 1

Animal models in which the hyaluronic acid capsule has been shown to enhance virulence of group A streptococci

Source: microbiolspec January 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0050-2018

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