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Chapter 4 : Capsular Polysaccharide of Group A Streptococci

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Abstract:

Careful observations by microbiologists and clinicians in the 1920s and 1930s pointed to a link between the hyaluronic acid capsule and group A streptococci (GAS) disease pathogenesis. More recent studies have defined the genetic locus that directs hyaluronic acid biosynthesis and have characterized the molecular mechanisms through which the capsule enhances GAS virulence. It is now appreciated that the capsule synthesis operon is both highly conserved and widely distributed among GAS strains, attesting to the adaptive role served by the hyaluronic acid capsule in the coevolution of GAS with the human host. As a poorly immunogenic “self” antigen, the capsular polysaccharide appears to have persisted in an invariant form in GAS. Studies of acapsular mutant strains have demonstrated that the capsule protects GAS from complement-mediated phagocytic killing and is essential for full virulence in a variety of experimental infection models. The GAS capsule also influences attachment of the bacteria to human epithelial cells, both by modulating interaction of M protein and other potential adhesins and by itself serving as a ligand for attachment of GAS to CD44 on epithelial cells. The successful adaptation of GAS to survival in the human host involves regulation of capsule expression that is dependent on the fine structure of the operon promoter, on the CsrRS two-component regulatory system, and, likely, on additional mechanisms yet to be uncovered.

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4

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FIGURE 1

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

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4
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Image of FIGURE 2
FIGURE 2

Map of the region of the GAS 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 IS1239′ is present approximately 50 nucleotides upstream of the operon promoter. (Adapted from the genome sequence of M1 strain SF370, GenBank accession number AE004092 [ ].)

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4
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Image of FIGURE 3
FIGURE 3

Diagram of the csrRS 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 [ ].)

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4
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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.

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4
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Tables

Generic image for table
TABLE 1

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

Citation: Wessels M. 2006. Capsular Polysaccharide of Group A Streptococci, p 37-46. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch4

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