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Chapter 4 : Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in

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Abstract:

In the developing world, is a major cause of pneumonia in young children, and the total worldwide mortality due to pneumococcal infections is approximately 1 to 2 million per year. The capsule is an integral part of the pneumococcal cell surface. The type 3 polysaccharide, as discussed, is not linked to the peptidoglycan but remains cell associated via a membrane lipid linkage or interactions with a membrane protein involved in its synthesis. The synthesis of all polysaccharides begins with the synthesis of nucleotide precursor sugars in the cytoplasm. Global control pathways affecting carbon metabolism may also be involved in the regulation of capsule synthesis. In particular, catabolite control protein A (CcpA) is an important regulator of the phosphoenolpyruvate-dependent phosphotransferase system that is the major system for sugar uptake in many bacteria. A mechanism for cleaving the chain has not been demonstrated but is predicted to be enzymatic based on the inability to introduce mechanical breaks without using sonication. The release of capsular polysaccharide may be important in pathogenesis, and the identification of an enzyme involved in this process will be an important step in understanding this role. Analyses of the genetics and biosynthesis of capsule production have yielded many important insights into one of the most important bacterial virulence factors. Understanding the regulatory mechanisms involved in capsule synthesis and release, and their integration with the synthesis of other surface structures, will thus be an important step in understanding the overall metabolism and virulence of the cell.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4

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Figures

Image of FIGURE 1
FIGURE 1

Linkage of the capsule and teichoic acid to peptidoglycan. The phosphodiester linkage of the capsule to GlcNAc is inferred by analogy to the linkage in ( ). The teichoic acid structure and linkage are based on data from references and . Sites of cleavage by mutanolysin and autolysin (LytA) are indicated by down and right arrows, respectively. AATGal, 2-acetamido-4-amino-2,4,6-trideoxy--Gal.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 2
FIGURE 2

Common pathways in the synthesis of cellular structures. Sugars common to the pathways of the type 2 and type 3 capsules, and other pathways, are shown. UDP-GlcNAc and AATGal (2-acetamido-4-amino-2,4,6-trideoxy--Gal) are used in the synthesis of capsules of other serotypes as well as peptidoglycan and teichoic acid, respectively. α--Glc is transported from the extracellular environment to the cytoplasm; lipid II is transported to the outer face of the cytoplasmic membrane for the polymerization of peptidoglycan. Choline-binding proteins are linked to the lipoteichoic acids ( ). Lipoteichoic acid exhibits the same repeat unit as teichoic acid ( Fig. 1 ) but is linked to the membrane via a Glc-AAT-Glc linkage to diacylglycerol ( ). Teichoic acid, the type 2 capsule, and other Wzy-dependent capsules are covalently linked to the peptidoglycan.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 3
FIGURE 3

Type 2 capsule structure (top) and genetic locus (bottom). The polymer is linked to Und-P in the membrane via the Glc residue in the backbone ( ). The type 2 genetic locus is flanked by the noncapsular genes and (also referred to as ) ( ). The common region contains genes found in all serotypes; the type-specific region contains genes unique to a given serotype. The genes predicted to encode the Wzy polymerase and the Wzx flippase (transporter) are indicated. The arrow indicates the predicted capsule operon. NDP, nucleotide diphosphate.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 4
FIGURE 4

The Wzy-dependent pathway for type 2 capsule synthesis. Synthesis begins with nucleotide precursor synthesis, shown in the lower right corner of the figure. The functions of enzymes in boxes and the order of action of the putative glycosyltransferases Cps2T, Cps2F, Cps2G, and Cps2I have not been experimentally demonstrated. Cps2J and Cps2H are the putative Wzx flippase and Wzy polymerase, respectively ( ). The functions of the type 19F homologues of the enzymes involved in TDP-Rha synthesis have been demonstrated previously ( ). After the transfer of a subunit or polymer, the C-P-P acceptor is expected to be cleaved to C-P and recycled to the inner face of the cytoplasmic membrane. It is not known whether the cleavage occurs on the inner or outer face of the membrane.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 5
FIGURE 5

Detection of capsule (CPS) and teichoic acid (TA) on immunoblots. The anti-capsule (α-CPS) blot was reacted with type 2 capsule-specific antiserum; the anti-teichoic acid blot was reacted with teichoic acid-specific antiserum. The protein molecular mass standards are for comparison between blots and do not represent polymer sizes. P, protoplast fraction; CW, cell wall fraction; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Methods and results are as described in reference .

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 6
FIGURE 6

Type 3 capsule biosynthetic pathway and genetic locus. The type 3 capsule genes are flanked by and (also referred to as ), as in the type 2 locus ( ). The 5′ end of is truncated (enclosure in parentheses indicates that the gene is mutated). The upstream common genes are not transcribed, and most are mutated ( ). is the homologue. is not homologous to but encodes the UDP-Glc dehydrogenase ( ). The boxed and (type 3 synthase) genes are the only genes in the locus that are necessary for type 3 capsule synthesis ( ). The locus is transcribed as an operon from through ( ). PGM and GalU are encoded outside the capsule locus ( ). is truncated and exhibits homology to IS ( ). , variable number.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 7
FIGURE 7

Model for type 3 capsule synthesis catalyzed by the type 3 synthase (Cps3S). Synthesis initiates on the cytoplasmic face of the membrane by the addition of Glc (ovals) to phosphatidylglycerol (triangles) and proceeds by the alternate addition of GlcUA (squares) and Glc.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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Image of FIGURE 8
FIGURE 8

Model for retention and release of the type 3 capsule. Release may occur following two breaks in the chain or the combination of a single break and ejection from the synthase, as shown in the right panel. Zipper-like symbols, phosphatidylglycerol; squares, Glc; circles, GlcUA.

Citation: Yother J. 2007. Integration of Capsular Polysaccharide Biosynthesis with Metabolic and Virulence Pathways in , p 51-66. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch4
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References

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1. Abeyta, M.,, G. G. Hardy, and, J. Yother. 2003. Genetic alteration of capsule type but not PspA type affects accessibility of surface-bound complement and surface antigens of Streptococcus pneumoniae. Infect. Immun. 71:218225.
2. Advisory Committee on Immunization Practices. 1997. Prevention of pneumococcal disease. Morb. Mortal. Wkly. Rep. 46:124.
3. Arrecubieta, C.,, E. Garcia, and, R. Lopez. 1995. Sequence and transcriptional analysis of a DNA region involved in the production of capsular polysaccharide in Streptococcus pneumoniae type 3. Gene 167:17.
4. Austrian, R. 1981. Some observations on the pneumococcus and on the current status of pneumococcal disease and its prevention. Rev. Infect. Dis. 3(Suppl):S1S17.
5. Avery, O. T., and, R. Dubos. 1931. The protective action of a specific enzyme against type III pneumococcus infection in mice. J. Exp. Med. 54:7389.
6. Bender, M. H.,, R. T. Cartee, and, J. Yother. 2003. Positive correlation between tyrosine phosphorylation of CpsD and capsular polysaccharide production in Streptococcus pneumoniae. J. Bacteriol. 185:60576066.
7. Bender, M. H., and, J. Yother. 2001. CpsB is a modulator of capsule-associated tyrosine kinase activity in Streptococcus pneumoniae. J. Biol. Chem. 276:4796647974.
8. Bentley, S. D.,, D. M. Aanensen,, A. Mavroidi,, D. Saunders,, E. Rabbinowitsch,, M. Collins,, K. Donohoe,, D. Harris,, L. Murphy,, M. A. Quail,, G. Samuel,, I. C. Skovsted,, M. S. Kaltoft,, B. Barrell,, P. R. Reeves,, J. Parkhill, and, B. G. Spratt. 2006. Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet. 2:e31.
9. Briles, D. E.,, M. J. Crain,, B. M. Gray,, C. Forman, and, J. Yother. 1992. Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae. Infect. Immun. 60:111116.
10. Briles, D. E.,, J. Horowitz,, L. S. McDaniel,, W. H. Benjamin, Jr.,, J. L. Claflin,, C. L. Booker,, G. Scott, and, C. Forman. 1986. Genetic control of susceptibility to pneumococcal infection. Curr. Top. Microbiol. Immunol. 124:103120.
11. Briles, D. E.,, M. Nahm,, K. Schoroer,, J. Davie,, P. Baker,, J. Kearney, and, R. Barletta. 1981. Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 Streptococcus pneumoniae. J. Exp. Med. 153:694705.
12. Brown, E. J.,, S. W. Hosea,, C. H. Hammer,, C. G. Burch, and, M. M. Frank. 1982. A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J. Clin. Investig. 69:8598.
13. Brown, E. J.,, K. A. Joiner,, R. M. Cole, and, M. Berger. 1983. Localization of complement component 3 on Streptococcus pneumoniae: anti-capsular antibody causes complement deposition on the pneumococcal capsule. Infect. Immun. 39:403409.
14. Bukantz, S. C.,, P. F. de Gara, and, J. G. M. Bullowa. 1942. Capsular polysaccharide in the blood of patients with pneumococcic pneumonia. Arch. Intern. Med. 69:191212.
15. Caimano, M. J.,, G. G. Hardy, and, J. Yother. 1998. Capsule genetics in Streptococcus pneumoniae and a possible role for transposition in the generation of the type 3 locus. Microbial Drug Resist. 4:1123.
16. Campbell, J. A.,, G. J. Davies,, V. Bulone, and, B. Henrissat. 1997. A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326:929942.
17. Cartee, R. T.,, W. T. Forsee,, M. H. Bender,, K. D. Ambrose, and, J. Yother. 2005. CpsE from type 2 Streptococcus pneumoniae catalyzes the reversible addition of glucose-1-phosphate to a polyprenyl phosphate acceptor, initiating type 2 capsule repeat unit synthesis. J. Bacteriol. 187:74257433.
18. Cartee, R. T.,, W. T. Forsee,, J. W. Jensen, and, J. Yother. 2001. Expression of the Streptococcus pneumoniae type 3 synthase in Escherichia coli: assembly of type 3 polysaccharide on a lipid primer. J. Biol. Chem. 276:4883148839.
19. Cartee, R. T.,, W. T. Forsee,, J. S. Schutzbach, and, J. Yother. 2000. Mechanism of type 3 capsular polysaccharide synthesis in Streptococcus pneumoniae. J. Biol. Chem. 275:39073914.
20. Cartee, R. T.,, W. T. Forsee, and, J. Yother. 2005. Initiation and synthesis of the Streptococcus pneumoniae type 3 capsule on a phosphatidylglycerol membrane anchor. J. Bacteriol. 187:44704479.
21. Chaffin, D. O.,, L. M. Mentele, and, C. E. Rubens. 2005. Sialylation of group B streptococcal capsular polysaccharide is mediated by cpsK and is required for optimal capsule polymerization and expression. J. Bacteriol. 187:46154626.
22. Darkes, M. J., and, G. L. Plosker. 2002. Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection. Paediatr. Drugs 4:609630.
23. Deng, L.,, D. L. Kasper,, T. P. Krick, and, M. R. Wessels. 2000. Characterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B Streptococcus. J. Biol. Chem. 275:74977504.
24. Dillard, J. P.,, M. W. Vandersea, and, J. Yother. 1995. Characterization of the cassette containing genes for type 3 capsular polysaccharide biosynthesis in Streptococcus pneumoniae. J. Exp. Med. 181:973983.
25. Dillard, J. P., and, J. Yother. 1994. Genetic and molecular characterization of capsular polysaccharide biosynthesis in Streptococcus pneumoniae type 3. Mol. Microbiol. 12:959972.
26. Fine, D. P. 1975. Pneumococcal type-associated variability in alternate complement pathway activation. Infect. Immun. 12:772778.
27. Finland, M., and, M. Barnes. 1977. Changes in occurrence of capsular serotypes of Streptococcus pneumoniae at Boston City Hospital during selected years between 1935 and 1974. J. Clin. Microbiol. 5:154166.
28. Fischer, W.,, T. Behr,, R. Hartmann,, J. Peter-Katalinic, and, H. Egge. 1993. Teichoic acid and lipoteichoic acid of Streptococcus pneumoniae have identical chain structures. A reinvestigation of teichoic acid (C-polysaccharide). Eur. J. Biochem. 215:851857.
29. Forsee, W. T.,, R. T. Cartee, and, J. Yother. 2000. Biosynthesis of type 3 capsular polysaccharide in Streptococcus pneumoniae: enzymatic chain release by an abortive translocation process. J. Biol. Chem. 275:2597225978.
30. Forsee, W. T.,, R. T. Cartee, and, J. Yother. 2006. Role of the carbohydrate binding site of the Streptococcus pneumoniae capsular polysaccharide type 3 synthase in the transition from oligosaccharide to polysaccharide synthesis. J. Biol. Chem. 281:62836289.
31. Giammarinaro, P., and, J. C. Paton. 2002. Role of RegM, a homologue of the catabolite repressor protein CcpA, in the virulence of Streptococcus pneumoniae. Infect. Immun. 70:54545461.
32. Grangeasse, C.,, P. Doublet,, E. Vaganay,, C. Vincent,, G. Deleage,, B. Duclos, and, A. J. Cozzone. 1997. Characterization of a bacterial gene encoding an autophosphorylating protein tyrosine kinase. Gene 204:259265.
33. Gray, B. G., and, J. H. C. Dillon. 1986. Clinical and epidemiologic studies of pneumococcal infection in children. Pediatr. Infect. Dis. 5:201207.
34. Griffith, F. 1928. The significance of pneumococcal types. J. Hyg. 27:113159.
35. Guidolin, A.,, J. K. Morona,, R. Morona,, D. Hansman, and, J. C. Paton. 1994. Nucleotide sequence analysis of genes essential for capsular polysaccharide biosynthesis in Streptococcus pneumoniae type 19F. Infect. Immun. 62:53845396.
36. Hardy, G. G.,, M. J. Caimano, and, J. Yother. 2000. Capsule biosynthesis and basic metabolism in Streptococcus pneumoniae are linked through the cellular phosphoglucomutase. J. Bacteriol. 182:18541863.
37. Hardy, G. G.,, A. D. Magee,, C. L. Ventura,, M. J. Caimano, and, J. Yother. 2001. Essential role for cellular phosphoglucomutase in virulence of type 3 Streptococcus pneumoniae. Infect. Immun. 69:23092317.
38. Henrichsen, J. 1995. Six newly recognized types of Streptococcus pneumoniae. J. Clin. Microbiol. 33:27592762.
39. Hostetter, M. K. 1986. Serotypic variations among virulent pneumococci in deposition and degradation of covalently bound C3b: implications for phagocytosis and antibody production. J. Infect. Dis. 153:682693.
40. Iannelli, F.,, B. J. Pearce, and, G. Pozzi. 1999. The type 2 capsule locus of Streptococcus pneumoniae. J. Bacteriol. 181:26522654.
41. Ilan, O.,, Y. Bloch,, G. Frankel,, H. Ullrich,, K. Geider, and, I. Rosenshine. 1999. Protein tyrosine phosphorylation kinases in bacterial pathogens are associated with virulence and production of exopolysaccharide. EMBO J. 18:32413248.
42. Jansson, P. E.,, B. Lindberg,, M. Anderson,, U. Lindquist, and, J. Henrichsen. 1988. Structural studies of the capsular polysaccharide from Streptococcus pneumoniae type 2, a reinvestigation. Carbohydr. Res. 182:111117.
43. Keenleyside, W. J., and, C. Whitfield. 1996. A novel pathway of O-polysaccharide biosynthesis in Salmonella enterica serovar Borreze. J. Biol. Chem. 271:2858128592.
44. Kelly, T.,, J. P. Dillard, and, J. Yother. 1994. Effect of genetic switching of capsular type on virulence of Streptococcus pneumoniae. Infect. Immun. 62:18131819.
45. Kim, J. O., and, J. N. Weiser. 1998. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J. Infect. Dis. 177:368377.
46. Lazarevic, V.,, P. Margot,, B. Soldo, and, D. Karamata. 1992. Sequencing and analysis of the Bacillus subtilis lytRABC divergon: a regulatory unit encompassing the structural genes of the Nacetylmuramoyl-L-alanine amidase and its modifier. J. Gen. Microbiol. 138:19491961.
47. Lesinski, G. B., and, M. A. Westerink. 2001. Vaccines against polysaccharide antigens. Curr. Drug Targets Infect. Disord. 1:325334.
48. Llull, D.,, E. García, and, R. López. 2001. Tts, a processive beta-glucosyltransferase of Streptococcus pneumoniae, directs the synthesis of the branched type 37 capsular polysaccharide in pneumococcus and other gram-positive species. J. Biol. Chem. 276:2105321061.
49. Llull, D.,, R. Munoz,, R. Lopez, and, E. Garcia. 1999. A single gene (tts) located outside the cap locus directs the formation of Streptococcus pneumoniae type 37 capsular polysaccharide. Type 37 pneumococci are natural, genetically binary strains. J. Exp. Med. 190:241251.
50. MacLeod, C. M.,, R. G. Hodges,, M. Heildeberger, and, W. G. Bernhard. 1945. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med. 82:445465.
51. MacLeod, C. M., and, M. R. Krauss. 1950. Relation of virulence of pneumococcal strains for mice to the quantity of capsular polysaccharide formed in vitro. J. Exp. Med. 92:19.
52. Magee, A. D., and, J. Yother. 2001. Requirement for capsule in colonization by Streptococcus pneumoniae. Infect. Immun. 69:37553761.
53. Mollerach, M.,, R. Lopez, and, E. Garcia. 1998. Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis. J. Exp. Med. 188:20472056.
54. Morona, J. K.,, R. Morona,, D. C. Miller, and, J. C. Paton. 2003. Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae. J. Bacteriol. 185:30093019.
55. Morona, J. K.,, R. Morona,, D. C. Miller, and, J. C. Paton. 2002. Streptococcus pneumoniae capsule biosynthesis protein CpsB is a novel manganese-dependent phosphotyrosine-protein phosphatase. J. Bacteriol. 184:577583.
56. Morona, J. K.,, R. Morona, and, J. C. Paton. 1997. Characterization of the locus encoding the Streptococcus pneumoniae type 19F capsular polysaccharide biosynthetic pathway. Mol. Microbiol. 23:751763.
57. Morona, J. K.,, J. C. Paton,, D. C. Miller, and, R. Morona. 2000. Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in Streptococcus pneumoniae. Mol. Microbiol. 35:14311442.
58. Mosser, J. L., and, A. Tomasz. 1970. Choline-containing teichoic acid as a structural component of pneumococcal cell wall and its role in sensitivity to lysis by an autolytic enzyme. J. Biol. Chem. 245:287298.
59. O’Brien, K. L., and, M. Santosham. 2004. Potential impact of conjugate pneumococcal vaccines on pediatric pneumococcal diseases. Am. J. Epidemiol. 159:634644.
60. Park, I. H.,, D. G. Pritchard,, R. Cartee,, A. Brandao,, M. C. C. Brandileone, and, M. H. Nahm. 2007. Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae. J. Clin. Microbiol. 45:12251233.
61. Ramos, A.,, I. C. Boels,, W. M. de Vos, and, H. Santos. 2001. Relationship between glycolysis and exopolysaccharide biosynthesis in Lactococcus lactis. Appl. Environ. Microbiol. 67:3341.
62. Sorensen, U. B.,, J. Henrichsen,, H. C. Chen, and, S. C. Szu. 1990. Covalent linkage between the capsular polysaccharide and the cell wall peptidoglycan of Streptococcus pneumoniae revealed by immunochemical methods. Microb. Pathog. 8:325334.
63. Thomas, J. D.,, P. Sideras,, C. I. Smith,, I. Vorechovsky,, V. Chapman, and, W. E. Paul. 1993. Co-localization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. Science 261:355358.
64. Titgemeyer, F., and, W. Hillen. 2002. Global control of sugar metabolism: a gram-positive solution. Antonie Leeuwenhoek 82:5971.
65. van Dam, J. E.,, A. Fleer, and, H. Snippe. 1990. Immunogenicity and immunochemistry of Streptococcus pneumoniae capsular polysaccharides. Antonie Leeuwenhoek 58:147.
66. Ventura, C. L.,, R. T. Cartee,, W. T. Forsee, and, J. Yother. 2006. Control of capsular polysaccharide chain length by UDP-sugar substrate concentrations in Streptococcus pneumoniae. Mol. Microbiol. 61:723733.
67. Vincent, C.,, P. Doublet,, C. Grangeasse,, E. Vaganay,, A. J. Cozzone, and, B. Duclos. 1999. Cells of Escherichia coli contain a protein-tyrosine kinase, Wzc, and a phosphotyrosine-protein phosphatase, Wzb. J. Bacteriol. 181:34723477.
68. Vollmer, W., and, A. Tomasz. 2000. The pgdA gene encodes for a peptidoglycan N-acetylglucosamine deacetylase in Streptococcus pneumoniae. J. Biol. Chem. 275:2049620501.
69. Weigel, P. H.,, V. C. Hascall, and, M. Tammi. 1997. Hyaluronan synthases. J. Biol. Chem. 272:1399714000.
70. Weiser, J. N.,, R. Austrian,, P. K. Sreenivasan, and, H. R. Masure. 1994. Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization. Infect. Immun. 62:25822589.
71. Weiser, J. N.,, D. Bae,, H. Epino,, S. B. Gordon,, M. Kapoor,, L. A. Zenewicz, and, M. Shchepetov. 2001. Changes in availability of oxygen accentuate differences in capsular polysaccharide expression by phenotypic variants and clinical isolates of Streptococcus pneumoniae. Infect. Immun. 69:54305439.
72. Whitfield, C. 2006. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75:3968.
73. Wicker, L. S., and, I. Scher. 1986. X-linked immune deficiency (xid) of CBA/N mice. Curr. Top. Microbiol. Immunol. 124:87101.
74. Winkelstein, J. A.,, A. S. Abramovitz, and, A. Tomasz. 1980. Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall. J. Immunol. 124:25022506.
75. Wugeditsch, T.,, A. Paiment,, J. Hocking,, J. Drummelsmith,, C. Forrester, and, C. Whit-field. 2001. Phosphorylation of Wzc, a tyrosine autokinase, is essential for assembly of group 1 capsular polysaccharides in Escherichia coli. J. Biol. Chem. 276:23612371.
76. Xayarath, B., and, J. Yother. 2007. Mutations blocking side chain assembly, polymerization, or transport of a Wzy-dependent Streptococcus pneumoniae capsule are lethal in the absence of suppressor mutations and can affect polymer transfer to the cell wall. J. Bacteriol. 189:33693381.
77. Yother, J.,, K. D. Ambrose, and, M. J. Caimano. 1997. Association of a partial H-rpt element with the type 3 capsule locus of Streptococcus pneumoniae. Mol. Microbiol. 25:201204.
78. Yother, J., and, J. M. White. 1994. Novel surface attachment mechanism of the Streptococcus pneumoniae protein PspA. J. Bacteriol. 176:29762985.

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