Chapter 3 : Capsules

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Recent years have seen a renewed interest in the characterization of the capsular polysaccharides of and many other bacteria. Many of the recent advances described in this chapter have their roots in classic studies of that have historical significance both for the pneumococcal field and, often, for biology as a whole. Confirmation of linkage of the genes involved in capsule synthesis and the first maps of capsule loci were obtained through recombination experiments. The presence of insertion sequence (IS) elements and nonfunctional genes (or gene fragments) is a common finding in the capsule loci, as already noted for the type 3 locus and the cryptic type 33F locus in type 37 strains. The essential nature of the capsule in virulence was established in early studies of , as described in the chapter. A role for capsule in colonization was demonstrated using the type 2 and type 3 strains that contain defined mutations in the capsule loci and in . Among clinical isolates of different capsular serotypes, levels of complement activation and deposition, as well as phagocytosis, vary in in vitro assays. As has long been the case, the capsules will continue to serve as paradigms for studies of virulence factors, immune responses, and polysaccharide biochemistry.

Citation: Yother J. 2004. Capsules, p 30-48. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch3
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Image of FIGURE 1

Repeating units of capsule structures. Capsule types for which the complete nucleotide sequence of the capsule locus has been published are shown. Where possible, the expected biological repeating unit is shown, based on initiation with glucose. The alternate glucose may be used in capsules containing more than one glucose. AATGal, 2-acetamido-4-amino-2,4,6-trideoxy--galactose; FucNAc, -acetylfucosamine; Gal, galactose; Glc, glucose; GlcNAc, -acetylglucosamine; GlcUA, glucuronic acid; Gly, glycerol; ManNAc, -acetylmannosamine; OAc, acetate; Rha, rhamnose; Rib, ribitol. References for chemical repeating units are as in reference 107.

Citation: Yother J. 2004. Capsules, p 30-48. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch3
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Image of FIGURE 2

Capsule genetic loci. The loci are shown for capsule types for which the complete nucleotide sequences have been published. For most loci, genes were named alphabetically in the order in which they occurred in the locus. Therefore, similarly named genes may not be homologous. Open boxes indicate type-specific genes, which encode glycosyltransferases, nucleotide sugar biosynthetic enzymes, and epimerases. Similarly shaded boxes are homologous. Sequences in parentheses are mutated compared to their respective homologs. The flanking gene in the downstream common region was originally identified as ( ) and later designated ( ) due to an apparent allelic difference between the two genes. However, and are the same; it is only in the type 3 locus that the gene is altered. , , and in the type 3 locus are also referred to as , , and , respectively ( ). in the type 3 locus is homologous to in the other loci. The type 4, 6B, and 18C genes were named according to the bacterial polysaccharide gene nomenclature system ( ) and are not referred to by the designations. For clarity, designations are shown here for the upstream common sequences and the TDP-Rha biosynthetic genes in these loci. The remainder of the letters are from the original designations. Differences in the - and -encoded polymerases are responsible for the different linkages in the polysaccharides ( ). Symbols: , conserved common sequences; , class I common sequences; , class II common sequences; and , initiating glycosyltransferases not homologous to class I or II; , Wzy homolog, putative polymerase; , Wzx homolog, putative flippase; , TDP-Rha biosynthesis. Classes of common sequences are based on reference 79. Arrows indicate putative or known transcription start sites and, where demonstrated, length of transcript. Some of the many IS elements and repetitive sequences (R) are indicated. Maps are derived from references , and .

Citation: Yother J. 2004. Capsules, p 30-48. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch3
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Image of FIGURE 3

Block-type (Wzy-dependent) synthesis. The repeat unit is for type 14. Functions for the glycosyltransferases CpsE, CpsG, CpsI, and CpsJ have been experimentally determined in the type 14 system ( ). CpsL and CpsH are the type 14 Wzx and Wzy homologs, respectively. PGM and GalU are the cellular enzymes and are not capsule specific. Functions of proteins in parentheses have not been experimentally demonstrated in the system. PGM, GalU, CpsG, CpsI, and CpsJ are located in the cytoplasm, whereas CpsE, CpsL, and CpsH are membrane associated. Following transfer of the chain, the lipid- P-P is hydrolyzed to lipid-P and recycled to the cytoplasmic face of the membrane.

Citation: Yother J. 2004. Capsules, p 30-48. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch3
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Image of FIGURE 4

Biosynthetic pathways for (A) dTDP-Rha synthesis in type 19F ( ) and (B) type 3 synthesis ( ). The type 3 synthase (Cps3S) is located in the membrane.

Citation: Yother J. 2004. Capsules, p 30-48. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch3
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