Chapter 3 : Biosynthesis and Genetics of the Capsule

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Until the late 1940s, little was known about cryptococcal capsule composition or structure. Classically, the capsule is described as composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins, based on the original fractionation of shed polysaccharide material. Cell wall polymers are involved in capsule association with the cell, although they are not considered part of the capsule itself. Polysaccharide synthesis starts with the generation of precursor molecules, the most common being the activated sugars discovered by Leloir. A number of proteins involved in the synthesis of these precursors have been identified and studied in . This work has been facilitated by the fact that many of these enzymes are highly conserved in terms of sequence, as would be expected from the participation of activated sugar precursors in multiple synthetic pathways across biology. In support of a lumenal location for capsule synthesis, a conditional mutant generated in both serotypes A and D that is defective in vesicle targeting to the plasma membrane accumulates post-Golgi vesicles containing GXM. The conclusion from this study is that GXM is made within the classical secretory pathway, consistent with the requirement for nucleotide sugar transporters to achieve normal capsule synthesis.

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 1

The capsule. (a) The capsule as drawn by Curtis in 1896 ( ). (b) India ink negative staining demonstrates the capsule as a zone of exclusion surrounding the cell. (c) Immunofluorescence microscopy of cryptococci after labeling with an anti-GXM monoclonal antibody. (d) Capsule quelling reaction that occurs when is mixed with anti-GXM monoclonal antibody as visualized by differential interference contrast microscopy. Reprinted, with permission, from reference . (e) Quickfreeze deepetch image of the edge of a budding cell. The plasma membrane (upper left) is separated by the cell wall from the fibrous capsule meshwork (extending toward lower right). Both wall and capsule surround both the parent cell and the emerging bud. Reprinted, with permission, from the cover image associated with reference . Cryptococcal cell bodies are typically 4 to 6 μm in diameter; the capsule can range from undetectable to ~30 μm in radius.

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 2

The six structural reporter groups of GXM defined by Cherniak et al. ( ). Mannose residues (shaded circles) are α-1,3-linked; xylose (stars) and glucuronic acid residues (half-filled diamonds) shown above the mannose backbone are β-1,2-linked; xylose shown below the backbone is β-1,4-linked. All sugars are in pyranose form, and mannose acetylation is not shown. Shapes follow the recommendations of the (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=glyco2). Modified, with permission, from reference .

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 3

The GalXM (GXMGal) structure. (Top) The structure of GalXM proposed by Vaishnav et al. ( ). (Bottom) The upper structure as revised by Heiss et al. ( ). The side branches that occur on every second galactose of the polymer backbone may be substituted on all three residues, on only the more distal two residues, on only the proximal two residues, or not at all ( ). The two extreme cases are shown. Symbols are as in Fig. 2 , with galactose shown as open circles and linkages as indicated. Modified, with permission, from reference .

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 4

Stimuli that lead to an alteration of the capsule size. Additional factors have been studied for their ability to modulate capsule but have a less marked effect. See text for details.

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 5

Reactivity of different GXM-specific monoclonal antibodies with two strains representative of serotypes A and D. Serial twofold dilutions were spotted (starting with 3 × 10 cells on the first spot at the top of each lane) on a nitrocellulose membrane and probed with a panel of anti-GXM monoclonal antibodies (designated A through E). Reprinted, with permission, from reference .

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 6

Nucleotide sugar metabolism in A simplified reaction scheme, highlighting synthetic steps discussed in the text. Plain text indicates biosynthetic intermediates; bold text on arrows indicates enzyme names; other bold text indicates nucleotide sugars.

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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Image of FIGURE 7

Cryptococcal vesicles. Two vesicle types observed in (Left) Vesicles of the classical secretory pathway fusing with the plasma membrane to release their cargo extracellularly. (Right) Vesicles formed within intracellular membrane-bound structures are released intact at the cell surface. Modified, with permission, from reference .

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3
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1. Bar-Peled, M., C. L. Griffith, and, T. L. Doering. 2001. Functional cloning and characterization of a UDP-gluc-uronic acid decarboxylase: the pathogenic fungus Cryptococcus neoformans elucidates UDP-xylose synthesis. Proc. Natl. Acad. Sci. USA 1 98: 1200312008.
2. Bar-Peled, M.,, C. L Griffith,, J. J. Ory, and, T. L. Doering. 2004. Biosynthesis of UDP-GlcA, a key metabolite for capsular polysaccharide synthesis in the pathogenic fungus Cryptococcus neoformans. Biochem. J. 381: 131136.
3. Benham, R. W. 1935. Cryptococci: their identification by morphology and by serology. J. Infect. Dis. 57: 255274.
4. Bennett, J. E., and, H. F. Hasenclever. 1965. Cryptococcus neoformans polysaccharide: studies on serologic properties and role in infection. J. Immunol. 94: 916920.
5. Bergman, F. 1965. Studies on capsule synthesis of Cryptococcus neoformans. Sabouraudia 4: 2331.
6. Berninsone, P. M., and, C. B. Hirschberg. 2000. Nucleotide sugar transporters of the Golgi apparatus. Curr. Opin. Struct. Biol. 10: 542547.
7. Beverley, S. M.,, K.L. Owens,, M. Showalter,, C. L Griffith,, T. L. Doering,, V. C. Jones,, and M. R. McNeil. 2005. Eukaryotic UDP-galactopyranose mutase ( GLF gene) in microbial and metazoal pathogens. Eukaryot. Cell 4: 11471154.
8. Bhattacharjee, A. K.,, K. J. Kwon-Chung, and, C. P. Glaudemans. 1978. On the structure of the capsular polysaccharide from Cryptococcus neoformans serotype C. Immunochemistry 15: 673679.
9. Bhattacharjee, A. K., K. J. Kwon-Chung, and, C. P. Glaudemans. 1979. The structure of the capsular polysaccharide from Cryptococcus neoformans serotype D. Carbohydr. Res. 73: 183192.
10. Bhattacharjee, A. K., K. J. Kwon-Chung, and, C. P. Glaudemans. 1979. On the structure of the capsular polysaccharide from Cryptococcus neoformans serotype C. II. Mol. Immunol. 16: 531532.
11. Bhattacharjee, A. K., K. J. Kwon-Chung, and, C. P. Glaudemans. 1980. Structural studies on the major capsular polysaccharide from Cryptococcus bacillisporus serotype B. Carbohydr. Res. 82: 103111.
12. Bhattacharjee, A. K., K. J. Kwon-Chung, and, C. P. J. Glaudemans. 1981. Capsulated polysaccharides from a parent strain and a possible, mutant strain of Cryptococcus neoformans serotype A. Carbohydr. Res. 95: 237248.
13. Bhattacharjee, A. K., J. E. Bennett, and, C. P. J. Glaudemans. 1984. Capsular polysaccharides of Cryptococcus neoformans. Rev. Infect. Dis. 6: 619624.
14. Blandamer, A., and, I. Danishefsky. 1966. Investigations on the structure of the capsular polysaccharide from Cryptococcus neoformans type B. Biochim. Biophys. Acta 117: 305313.
15. Bose,, I.,, A.J. Reese,, J.J. Ory,, G. Janbon,, and T. L. Doering. 2003. A yeast under cover: the capsule of Cryptococcus neoformans. Eukaryot. Cell. 2: 655663.
16. Buchanan, K. L., and, J. W. Murphy. 1998. What makes Cryptococcus neoformans a pathogen? Emerg. Infect. Dis. 4: 7183.
17. Bulmer, G. S., M. D. Sans, and, C. M. Gunn. 1967. Cryptococcus neoformans. I. Nonencapsulated mutants. J. Bacteriol. 94: 14751479.
18. Bülter, T., and, L. Elling. 1999. Enzymatic synthesis of nucleotide sugars. Glycoconj. J. 16: 147159.
19. Busse, O. 1894. Ueber parasitärezellen schlüsse und thre zuchtung. Centralbl. Bakt. Parasit. 16: 175180.
20. Casadevall, A., and, J. R. Perfect. 1998. Cryptococcus neoformans. ASM Press, Washington, DC.
21. Castle, S. A.,, E.A. Owuor,, S.H. Thompson,, M. R Garnsey,, J. S. Klutts,, T. L. Doering,, and S. B. Levery. 2008. β1,2-Xylosyltransferase Cxt1p is solely responsible for xylose incorporation into Cryptococcus neoformans glycosphingolipids. Eukaryot. Cell 7: 16111615.
22. Chang, Y. C., and, K. J. Kwon-Chung. 1994. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol. Cell. Biol. 14: 49124919.
23. Chang, Y. C., L. A. Penoyer, and, K. J. Kwon-Chung. 1996. The second capsule gene of Cryptococcus neoformans, CAP64, is essential for virulence. Infect. Immun. 64: 19771983.
24. Chang, Y. C., and, K. J. Kwon-Chung. 1998. Isolation of the third capsule-associated gene CAP60, required for virulence in Cryptococcus neoformans. Infect. Immun. 66: 22302236.
25. Chang, Y. C., and, K. J. Kwon-Chung. 1999. Isolation, characterization, and localization of a capsule-associated gene, CAP10, of Cryptococcus neoformans. J. Bacteriol. 181: 56365643.
26. Chang, Y. C.,, A. Jong, S. Huang,, P. Zerfas,, and K. J. Kwon-Chung. 2006. CPS1, a homolog of the Streptococcus pneumoniae type 3 polysaccharide synthase gene, is important for the pathobiology of Cryptococcus neoformans. Infect. Immun. 74: 39303938.
27. Charlier, C.,, F. Chretien,, M. Baudrimont,, E. Mordelet,, O. Lortholary,, and F. Dromer. 2005. Capsule structure changes associated with Cryptococcus neoformans crossing of the blood-brain barrier. Am. J. Pathol. 166: 421432.
28. Cherniak, R.,, E. Reiss,, M.E. Slodki,, R.D. Plattner,, and S. O. Blumer. 1980. Structure and antigenic activity of the capsular polysaccharide of Cryptococcus neoformans serotype A. Mol. Immunol. 17: 10251032.
29. Cherniak, R., E. Reiss, and, S. H. Turner. 1982. A galactomannan antigen of Cryptococcus neoformans serotype A. Carbohydr. Res. 103: 239250.
30. Cherniak, R.,, L. C Morris,, B. C. Anderson, and, S. A. Meyer. 1991. Facilitated isolation, purification and analysis of glucuronoxylomannan of Cryptococcus neoformans. Infect. Immun. 59: 5964.
31. Cherniak, R., and, J. B. Sundstrom. 1994. Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect. Immun. 62: 15071512.
32. Cherniak, R.,, L. C. Morris,, T. Belay, E. D. Spitzer,, and A. Casadevall. 1995. Variation in the structure of glucuronoxylomannan in isolates from patients with recurrent cryptococcal meningitis. Infect. Immun. 63: 18991905.
33. Cherniak, R.,, H. Valafar,, L.C. Morris,, and F. Valafar. 1998. Cryptococcus neoformans chemotyping by quantitative analysis 1H nuclear magnetic resonance spectra of glucuronoxylomannans with a computer-simulated artificial neural network. Clin. Diagn. Lab. Immunol. 5: 146159.
34. [Reference deleted.]
35. Chretien, F.,, O. Lortholary,, I. Kansau, S. Neuville, F. Gray,, and F. Dromer. 2002. Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia. J. Infect. Dis. 186: 522530.
36. Cleare, W., R. Cherniak, and, A. Casadevall. 1999. In vitro and in vivo stability of Cryptococcus neoformans glucuronoxylomannan epitope that elicits protective antibodies. Infect. Immun. 67: 30963107.
37. Corradini, C.,, G. Canali,, A. Cavazza, D. Delfino,, and G. Teti. 1998. Compositional analysis of the major capsular polysaccharides of Cryptococcus neoformans by high performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). J. L. Chromatogr. Related Technol. 21: 941951.
38. Cottrell, T. R.,, C.L. Griffith,, H. Liu, A. A. Nenninger,, and T. L. Doering. 2007. The pathogenic fungus Cryptococcus neoformans expresses two functional GDP-mannose transporters with distinct expression patterns and roles in capsule synthesis. Eukaryot. Cell 6: 776785.
39. Coutinho, P. M.,, E. Deleury,, G.J. Davis,, and B. Henrissat. 2003. An evolving hierarchical family classification for glycosyltransferases. J. Mol. Evol. 328: 307317.
40. Curtis, F. 1896. Contribution à l’étude de la saccharomycose humaine. Ann. Inst. Pasteur 15: 449468.
41. Daude,, N.,, T.K. Gallaher,, M. Zeschnigk, A. Starzinski-Powitz,, K. G. Petry, I. S. Haworth,, and J. K. Reichardt. 1995. Molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4’-epimerase. Biochem. Mol. Med. 56: 17.
42. Dean, N., Y. B. Zhang, and, J. B. Poster. 1997. The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae. J. Biol. Chem. 272: 3190831914.
43. Doering, T. L. 1999. A unique α-1,3 mannosyltransferase of the pathogenic fungus Cryptococcus neoformans. J. Bacteriol. 181: 54825488.
44. Doering, T. L. 2000. How does Cryptococcus get its coat? Trends Microbiol. 8: 547553.
45. Doering, T. L. 2009. How sweet it is! Capsule formation and cell wall biogenesis in Cryptococcus neoformans. Ann. Rev. Microbiol. 63: 223247.
46. Drouhet, E., G. Secretain, and, J. P. Aubert. 1950. Polyoside capsulaire d’un champignon pathogene Torulopsis neoformans relation avec la virulence. Ann. Inst. Pasteur 79: 891900.
47. Drouhet, E., and, G. Secretain. 1951. Inhibition de la migration leucocytaire in vitro par un polyoside capsulaire de Torulopsis ( Cryptococcus) neoformans. Ann. Inst. Pasteur 81: 674676.
48. Dykstra, M. A., L. Friedman, and, J. W. Murphy. 1977. Capsule size of Cryptococcus neoformans: control and relationship to virulence. Infect. Immun. 16: 129135.
49. Eigenheer, R. A.,, Y. Jin Lee,, E. Blumwald,, B. S. Phinney,, and A. Gelli. 2007. Extracellular glycosylphosphati-dylinositol-anchored mannoproteins and proteases of Cryptococcus neoformans. FEMS Yeast Res. 7: 499510.
50. Ellerbroek, P. M.,, D.J. Lefeber,, R. van Veghel,, J. Scharringa,, E. Brouwer,, G. J Gerwig,, G. Janbon,, A. I. Hoepelman,, and F. E. Coenjaerts. 2004. O-acetylation of cryptococcal capsular glucuronoxylomannan is essential for interference with neutrophil migration. J. Immunol. 173: 75137520.
51. Evans, E. E. 1949. An immunologic comparison of twelve strains of Cryptococcus neoformans ( Torula histoytica). Proc. Soc. Exp. Biol. Med. 71: 644646.
52. Evans, E. E. 1950. The antigenic composition of Cryptococcus neoformans. J. Immunol. 64: 423430.
53. Evans, E. E., and, J. W. Mehl. 1950. A qualitative analysis of capsular polysaccharides from Cryptococcus neoformans by filter paper chromatography. Science 114: 1011.
54. Falkow, S. 1988. Molecular Koch’s postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10: 52745276.
55. Farhi, F., G. S. Bulmer, and, J. R. Tacker. 1970. Cryptococcus neoformans. IV. The not-so-encapsulated yeast. Infect. Immun. 1: 526531.
56. Franzot, S. P.,, J. Mukherjee,, R. Cherniak,, L. Chen,, J. S. Hamdan,, and A. Casadevall. 1998. Microevolution of a standard strain of Cryptococcus neoformans resulting in differences in virulence and other phenotypes. Infect. Immun. 66: 8997.
57. Frases, S.,, L. Nimrichter,, N. B. Viana,, A. Nakouzi,, and A. Casadevall. 2008. Cryptococcus neoformans capsular polysaccharide and exopolysaccharide fractions manifest physical, chemical, and antigenic differences. Eukaryot. Cell. 7: 319327.
58. Frases, S.,, B. Pontes,, L. Nimrichter,, N. B. Viana,, M. L. Rodrigues,, and A. Casadevall. 2009. Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules. Proc. Natl. Acad. Sci. USA 106: 12281233.
59. Fries, B. C.,, D. L. Goldman,, R. Cherniak,, R. Ju,, and A. Casadevall. 1999. Phenotypic switching in Cryptococcus neoformans results in changes in cellular morphology and glucuronoxylomannan structure. Infect. Immun. 67: 60766083.
60. Fries, B. C.,, C. P. Taborda,, E. Serfass,, and A. Casadevall. 2001. Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection. J. Clin. Invest. 108: 16391648.
61. Fries, B. C.,, S.C. Lee,, R. Kennan,, W. Zhao,, A. Casadevall,, and D. L. Goldman. 2005. Phenotypic switching of Cryptococcus neoformans can produce variants that elicit increased intracranial pressure in a rat model of cryptococcal meningoencephalitis. Infect. Immun. 73: 17791787.
62. Gadebusch, H. H., P. A. Ward, and, E. P. Frenkel. 1964. Natural host resistance to infection with Cryptococcus neoformans. III. The effect of cryptococcal polysacharide upon physiology of the reticuloendothelial system of laboratory animals. J. Infect. Dis. 114: 95106.
63. Garcia-Hermoso, D., F. Dromer, and, G. Janbon. 2004. Cryptococcus neoformans capsule structure evolution in vitro and during murine infection. Infect. Immun. 72: 33593365.
64. García-Rivera, J.,, Y. C. Chang,, K. J. Kwon-Chung,, and A. Casadevall. 2004. Cryptococcus neoformans CAP59 (or Cap59p) is involved in the extracellular trafficking of capsular glucuronoxylomannan. Eukaryot. Cell 3: 385392.
65. Gates, M. A., P. Thorkildson, and, T. R. Kozel. 2004. Molecular architecture of the Cryptococcus neoformans capsule. Mol. Microbiol. 52: 1324.
66. Girrbach, V., and, S. Strahl. 2003. Members of the evolutionary conserved PMT family of protein O-mannosyltrans-ferases from distinct protein complexes among themselves. J. Biol. Chem. 278: 1255412562.
67. Goldman, D. L.,, B. C. Fries,, S. P. Franzot,, L. Montella,, and A. Casadevall. 1998. Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with change in virulence and pulmonary inflammatory response in rodents. Proc. Natl. Acad. Sci. USA 95: 1496714972.
68. Granger, D. L., J. R. Perfect, and, D. T. Durack. 1985. Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J. Clin. Invest. 76: 508516.
69. Griffith, C. L.,, J.S. Klutts,, L. Zhang, S. B. Levery,, and T. L. Doering. 2004. UDP-glucose dehydrogenase plays multiple roles in the biology of the pathogenic fungus Cryptococcus neoformans. J. Biol. Chem. 279: 5166951676.
70. Gutierrez, A. L.,, L. Farage,, M. N. Melo,, R.S. Mohana-Borges,, Y. Guerardel,, B. Coddeville,, J. M Wieruszeski,, L. Mendonça-Previato,, and J. O. Previato. 2007. Characterization of glycoinositolphosphoryl ceramide structure mutant strains of Cryptococcus neoformans. Glycobiology 17: 1C11C.
71. Harper, A. D., and, M. Bar-Peled. 2002. Biosynthesis of UDP-xylose. Cloning and characterization of a novel Arabidopsis gene family, UXS, encoding soluble and putative membrane-bound UDP-glucuronic acid decarboxylase isoforms. Plant Physiology 130: 21882198.
72. Heise, N.,, A. L. Gutierrez,, K. A. Mattos,, C. Jones,, R. Wait,, J. O. Previato,, and L. Mendonça-Previato. 2002. Molecular analysis of a novel family of complex glycoinositolphosphoryl ceramides from Cryptococcus neoformans: structural differences between encapsulated and acapsular yeast forms. Glycobiology 12: 409420.
73. Heiss, C.,, J. S. Klutts,, Z. Wang, T. L. Doering,, and P. Azadi. 2009. The structure of Cryptococcus neoformans galactoxylomannan contains beta-D-glucuronic acid. Carbohydr. Res. 344: 915920.
74. Hirschberg, C. B.,, P.W. Robbins,, and C. Abeijon. 1998. Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu. Rev. Biochem. 67: 4969.
75. Holden, H. M., I. Rayment, and, J. B. Thoden. 2003. Structure and function of enzymes of the Leloir pathway for galactose metabolism. J. Biol. Chem. 278: 4388543888.
76. Jacobson, E. S.,, D.J. Ayers,, A.C. Harrel,, and C. C. Nicholas. 1982. Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans. J. Bacteriol. 150: 12921296.
77. Jacobson, E. S., and, W. R. Payne. 1982. UDP-glucuronate decarboxylase and synthesis of capsular polysaccharide in Cryptococcus neoformans. J. Bacteriol. 152: 932934.
78. Jacobson, E. S. 1987. Cryptococcal UDP-glucose dehydrogenase: enzymatic control of capsular biosynthesis. J. Med. Vet. Mycol. 25: 131135.
79. Jacobson, E. S., M. J. Tingler, and, P. L. Quynn. 1989. Effect of hypersolutes upon the polysaccharide capsule in Cryptococcus neoformans. Mycoses 32: 1423.
80. James, P. G., and, R. Cherniak. 1992. Galactoxylomannans of Cryptococcus neoformans. Infect. Immun. 60: 10841088.
81. Janbon, G.,, U. Himmelreich,, F. Moyrand, L. Improvisi,, and F. Dromer. 2001. Cas1p is a membrane protein necessary for the O-acetylation of the Cryptococcus neoformans capsular polysaccharide. Mol. Microbiol. 42: 453467.
82. Janbon, G. 2004. Cryptococcus neoformans capsule biosynthesis and regulation. FEMS Yeast Res. 48: 765771.
83. Jong,, A.,, C.H. Wu,, H.M. Chen,, F. Luo,, K. J. Kwon-Chung,, Y. C Chang,, C. W. Lamunyon,, A. Plaas,, and S. H. Huang. 2007. Identification and characterization of CPS1 as a hyaluronic acid synthase contributing to the pathogenesis of Cryptococcus neoformans infection. Eukaryot. Cell. 6: 14861496.
84. Jong,, A.,, C.H. Wu,, G.M. Shackleford,, K.J. Kwon-Chung,, Y. C Chang,, H. M. Chen,, Y. Ouyang,, and S. H. Huang. 2008. Involvement of human CD44 during Cryptococcus neoformans infection of brain microvascular endothelial cells. Cell. Microbiol. 10: 13131326.
85. Jungmann, J., and, S. Munro. 1998. Multiprotein complexes in the cis Golgi of Saccharomyces cerevisiae with a-1,6-mannosyltransferase activity. EMBO J. 17: 423434.
86. Kligman, A. M. 1947. Studies of the capsular substance of Torula histolytica and the immunologic properties of Torula cells. J. Immunol. 57: 395401.
87. Klutts, J. S.,, A. Yoneda, M. C. Reilly,, I. Bose,, and T. L. Doering. 2006. Glycosyltransferases and their products: cryptococcal variations on fungal themes. FEMS Yeast Res. 6: 499512.
88. Klutts, J. S., S. B. Levery, and, T. L. Doering. 2007. A beta-1,2-xylosyltransferase from Cryptococcus neoformans defines a new family of glycosyltransferases. J. Biol. Chem. 282: 1789017899.
89. Klutts, J. S., and, T. L. Doering. 2008. Cryptococcal xy-losyltransferase 1 (Cxt1p) from Cryptococcus neoformans plays a direct role in the synthesis of capsule polysaccharides. J. Biol. Chem. 283: 1432714334.
90. Kozel, T. R., and, J. Cazin, Jr. 1971. Nonencapsulated variant of Cryptococcus neoformans. Infect. Immun. 3: 287294.
91. Kozel, T. R. 1995. Virulence factors of Cryptococcus neoformans. Trends Microbiol. 3: 295299.
92. Kozel, T. R.,, S. M. Levitz,, F. Dromer,, M. A. Gates,, P. Thorkildson,, and G. Janbon. 2003. Antigenic and biological characteristics of mutant strains of Cryptococcus neoformans lacking capsular O-acetylation or xylosyl side chains. Infect. Immun. 71: 28682875.
93. Lairson, L. L.,, B. Henrissat, G. J. Davies,, and S. G. Withers. 2008. Glycosyltransferases: structures, functions, and mechanisms. Annu. Rev. Biochem. 77: 521555.
94. Leloir, L. F. 1970. Two decades of research on the biosynthesis of saccharides. Science 172: 12991303.
95. Lengeler, K. B., D. Tielker, and, J. F. Ernst. 2008. Protein-O-mannosyltransferases in virulence and development. Cell. Mol. Life Sci. 65: 528544.
96. Levitz, S. M.,, S. Nong, M. K. Mansour,, C. Huang,, and C. A. Specht. 2001. Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T-cell responses to Cryptococcus neoformans. Proc. Natl. Acad. Sci. USA 98: 1042210427.
97. Littman, M. L. 1958. Capsule synthesis by Cryptococcus neoformans. Trans. N.Y. Acad. Sci. 20: 623648.
98. Liu, O. W.,, M.J. Kelly,, E.D. Chow,, and H. D. Madhani. 2007. Parallel beta-helix proteins required for accurate capsule polysaccharide synthesis and virulence in the yeast Cryptococcus neoformans. Eukaryot. Cell 6: 630640.
99. Liu, O. W.,, C.D. Chun,, E.D. Chow,, C. Chen,, H. D. Madhani,, and S. M. Noble. 2008. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135: 174188.
100. Loftus, B.,, E. Fung,, P. Roncaglia, D. Rowley,, P. Amedeo,, D. Bruno,, J. Vamathevan,, M. Miranda,, I. Anderson,, J. A Fraser,, J. Allen,, I. Bosdet,, M. R Brent,, R. Chiu,, T. L Doering,, M. J. Donlin,, C. A. D’Souza,, D. S Fox,, V. Grinberg,, J. Fu,, M. Fukushima,, B. Haas,, J. C Huang,, G. Janbon,, S. Jones,, M. I Krzywinski,, K. J. Kwon-Chung,, K. B Lengeler,, R. Maiti,, M. Marra,, R. E Marra,, C. Mathewson,, T. G Mitchell,, M. Pertea,, F. Riggs,, S. L Salzberg,, J. Schein,, A. Shvartsbeyn,, H. Shin,, C. Specht,, B. Suh,, A. Tenney,, T. Utterback,, B. L Wickes,, N. Wye,, J. W Kronstad,, J. K. Lodge,, J. Heitman,, R. W Davis,, C. M. Fraser,, and R. W. Hyman. 2005. The genome and transcriptome of Cryptococcus neoformans, a basidiomycetous fungal pathogen of humans. Science 307: 13211324.
101. López-Lara, I. M.,, D. Kafetzopoulos,, H. P. Spaink, and, J. E. Thomas-Oates. 2001. Rhizobial NodL O-acetyl transferase and NodS N-methyl transferase functionally interfere in production of modified Nod factors. J. Bacte-riol. 183: 34083416.
102. Love, G. L., G. D. Boyd, and, D. L. Greer. 1985. Large Cryptococcus neoformans from brain abscess. J. Clin. Microbiol. 22: 10681070.
103. Luberto, C.,, D. L. Toffaletti,, E. A. Wills,, S. C. Tucker,, A. Casadevall,, J. R. Perfect,, Y. A. Hannun,, and M. Del Poeta. 2001. Roles for inositolphosphoryl ceramide synthase 1 ( IPC1) in pathogenesis of C. neoformans. Genes Dev. 12: 201212.
104. Luberto, C.,, B. Martinez-Marino,, D. Taraskiewicz,, B. Bolanos,, P. Chitano,, D. Toffaletti,, G. Cox,, J. Perfect,, Y. Hannun,, E. Balish,, and M. Del Poeta. 2003. Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans. J. Clin. Invest. 112: 10801094.
105. Lussier, M.,, A.M. Sdicu, and, H. Bussey. 1999. The KTR and MNN1 mannosyltransferase families of Saccharomyces cerevisiae. Biochim. Biophys. Acta 1426: 323334.
106. Mager, J., and, M. Aschner. 1947. Biological studies on capsulated yeasts. J. Bacteriol. 53: 283295.
107. McFadden, D. C., and, A. Casadevall. 2004. Unexpected diversity in the fine specificity of monoclonal antibodies that use the same V region gene to glucuronoxylomannan of Cryptococcus neoformans. J. Immunol. 172: 36703677.
108. McFadden, D. C.,, M. De Jesus, and, A. Casadevall. 2006. The physical properties of the capsular polysaccharides from Cryptococcus neoformans suggest features for capsule construction. J. Biol. Chem. 281: 18681875.
109. McFadden, D. C.,, B. C. Fries,, F. Wang,, and A. Casadevall. 2007. Capsule structural heterogeneity and antigenic variation in Cryptococcus neoformans. Eukaryot. Cell 6: 14641473.
110. Merrifield, E. H., and, A. M. Stephen. 1980. Structural investigations of two capsular polysaccharides from Cryptococcus neoformans. Carbohydr. Res. 86: 6976.
111. Mille,, C.,, P. Bobrowicz,, P.A. Trinel,, H. Li,, E. Maes,, Y. Guerardel,, C. Fradin,, M. Martínez-Esparza,, R. C. Davidson,, G. Janbon,, D. Poulain,, and S. Wildt. 2008. Identification of a new family of genes involved in β1,2-mannosylation of glycans in Pichia pastoris and Candida albicans. J. Biol. Chem. 283: 97249736.
112. Miyazaki, T. 1961. Studies on fungal polysaccharides. III. Chemical structure of the capsular polysaccharide from Cryptococcus neoformans. Chem. Pharm. Bull. 9: 829833.
113. Moyrand, F.,, B. Klaproth,, U. Himmelreich, F. Dromer,, and G. Janbon. 2002. Isolation and characterization of capsule structure mutant strains of Cryptococcus neoformans. Mol. Microbiol. 45: 837849.
114. Moyrand, F.,, Y. C. Chang,, U. Himmelreich, K. J. Kwon-Chung,, and G. Janbon. 2004. Cas3p belongs to a seven member family of capsule structure designer proteins. Eukaryot. Cell 3: 15131524.
115. Moyrand, F., and, G. Janbon. 2004. UGD1 encoding the Cryptococcus neoformans UDP-glucose dehydrogenase is essential for growth at 37°C and for capsule biosynthesis. Eukaryot. Cell 3: 16011608.
116. Moyrand, F., T. Fontaine, and, G. Janbon. 2007. Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol. Microbiol. 64: 771781.
117. Moyrand, F.,, I. Lafontaine,, T. Fontaine,, and G. Janbon. 2008. UGE1 and UGE2 regulate the UDP-glucose/UDP-galactose equilibrium in Cryptococcus neoformans. Eukaryot. Cell 7: 20692077.
118. Murphy, J. W. 1998. Protective cell-mediated immunity against Cryptococccus neoformans. Res. Immunol. 149: 373386.
119. Nimmich, W. 1968. Isolation and qualitative component analysis of Klebsiella K-antigens. Z. Med. Mikrobiol. Immunol. 154: 117131.
120. Nimrichter, L.,, S. Frases,, L.P. Cinelli,, N.B. Viana,, A. Nakouzi,, L. R Travassos,, A. Casadevall,, and M. L. Rodrigues. 2007. Self-aggregation of Cryptococcus neoformans capsular glucuronoxylomannan is dependent on divalent cations. Eukaryot. Cell 6: 14001410.
121. Norambuena, L.,, L. Marchant,, P. Berninsone,, C. B. Hirschberg,, H. Silva,, and A. Orellana. 2002. Transport of UDP-galactose in plants. Identification and functional characterization of AtUTr1, an Arabidopsis thaliana UDP-galactose/UDP-glucose transporter. J. Biol. Chem. 277: 3292332929.
122. Pierini, L. M., and, T. L. Doering. 2001. Spacial and temporal sequence of capsule construction in Cryptococcus neoformans. Mol. Microbiol. 41: 105115.
123. Rebers, P. A.,, S.A. Barker,, M. Heidelberger, Z. Dische,, and E. E. Evans. 1958. Precipitation of the specific polysaccharide of Cryptococcus neoformans A by types II and XIV antipneumococcal sera. J. Am. Chem. Soc. 80: 11351137.
124. Reese, A. J., and, T. L. Doering. 2003. Cell wall α-1,3-glucan is required to anchor the Cryptococcus neoformans capsule. Mol. Microbiol. 50: 14011409.
125. Reese, A. J.,, A. Yoneda, J. A. Breger,, A. Beauvais,, H. Liu,, C. L Griffith,, I. Bose,, M. J Kim,, C. Skau,, S. Yang,, J. A Sefko,, M. Osumi,, J. P Latge,, E. Mylonakis,, and T. L. Doering. 2007. Loss of cell wall alpha(1–3) glucan affects Cryptococcus neoformans from ultrastructure to virulence. Mol. Microbiol. 63: 13851398.
126. [Reference deleted.]
127. Reiter, W. D., and, G. F. Vanzin. 2001. Molecular genetics of nucleotide sugar interconversion pathways in plants. Plant Mol. Biol. 47: 95113.
128. Rivera, J.,, M. Feldmesser,, M. Cammer,, and A. Casadevall. 1998. Organ-dependent variation of capsule thickness in Cryptococcus neoformans during experimental murine infection. Infect. Immun. 66: 50275030.
129. Rodrigues, M. L.,, L. Nimrichter,, D. L. Oliveira,, S. Frases,, K. Miranda,, O. Zaragoza,, M. Alvarez,, A. Nakouzi,, M. Feldmesser,, and A. Casadevall. 2007. Vesicular poly-saccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport. Eukaryot. Cell 6: 4859.
130. Rodrigues, M. L.,, M. Alvarez,, F.L. Fonseca,, and A. Casadevall. 2008. Binding of the wheat germ lectin to Cryptococcus neoformans suggests an association of chitinlike structures with yeast budding and capsular glucuronoxylomannan. Eukaryot. Cell 7: 602609.
131. Rodrigues, M. L.,, E. S. Nakayasu,, D. L. Oliveira,, L. Nimrichter,, J. D. Nosanchuk,, I. C. Almeida,, and A. Casadevall. 2008. Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. Eukaryot. Cell 7: 5867.
132. Sanfelice, F. 1894. Contributo alla morphologia e biologica dei blastomiceti che sisciluppano nei succhi di alcuni frutti. Ann. Ist. Ig. R. Univ. Roma 4: 463469.
133. Sanfelice, F. 1895. Ueber einen neuen pathogenen Blastomyceten, welcher innerhalb der Gewebe unter Bildung kalkartig aussehender Massen degeneriert. Zentralbl. Bakt. Parasit. 18: 521526.
134. Soll, D. R. 1992. High-frequency switching in Candida albicans. Clin. Microbiol. Rev. 5: 183203.
135. Sommer, U., H. Liu, and, T. L. Doering. 2003. An α-1,3-mannosyltransferase of Cryptococcus neoformans. J Biol Chem 278: 4772447730.
136. Still, C. N., and, E. S. Jacobson. 1983. Recombinational mapping of capsule mutations in Cryptococcus neoformans. J. Bacteriol. 156: 460462.
137. Strahl-Bolsinger, S., M. Gentzsch, and, W. Tanner. 1999. Protein O-mannosylation. Biochim. Biophys. Acta 1426: 297307.
138. Sumner, E. R., and, S. V. Avery. 2002. Phenotypic heterogeneity: differential stress resistance among individual cells of the yeast Saccharomyces cerevisiae. Microbiology 148: 345351.
139. Sun-Wada, G. H.,, S. Yoshioka,, N. Ishida,, and M. Kawakita. 1998. Functional expression of the human UDP-galactose transporters in the yeast Saccharomyces cerevisiae. J. Biochem. 123: 912917.
140. Tucker, S. C., and, A. Casadevall. 2002. Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm. Proc. Natl. Acad. Sci. USA 99: 31653170.
141. Turner, S. H.,, R. Cherniak, and, E. Reiss. 1984. Fractionation and characterization of galactoxylomannan from Cryptococcus neoformans. Carbohydr. Res. 125: 343349.
142. Turner, S. H., and, R. Cherniak. 1991. Multiplicity in the structure of the glucuronoxylomannan of Cryptococcus neoformans, p. 123–142. In J. P. Latgé and D. Boucias (ed.), Fungal Cell Wall and Immune Response. NATO ASI Series, Heidelberg, Germany.
143. Turner, S. H.,, R. Cherniak,, E. Reiss, and, K. J. Kwon-Chung. 1992. Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C-NMR spectroscopy. Carbohydr. Res. 233: 205218.
144. Vaishnav, V. V.,, B. E. Bacon,, M. O’Neill,, and R. Cherniak. 1998. Structural characterization of the galactoxy-lomannan of Cryptococcus neoformans Cap67. Carbohydr. Res. 306: 315330.
145. Vartivarian, S. E.,, E.J. Anaissie,, R.E. Cowart,, H. A Sprigg,, M. J. Tingler,, and E. S. Jacobson. 1993. Regulation of cryptococcal capsular polysaccharide by iron. J. Infect. Dis. 167: 186190.
146. Vecchiarelli, A. 2000. Immunoregulation by capsular components of Cryptococcus neoformans. Med. Mycol. 38: 407417.
147. White, C. W., R. Cherniak, and, E. S. Jacobson. 1990. Side group addition by xylosyltransferase and glucuron-yltransferase in the biosynthesis of capsular polysaccharide in Cryptococcus neoformans. J. Med. Vet. Mycol. 28: 289301.
148. Wills, E. A.,, I.S. Roberts,, M. Del Poeta,, J. Rivera,, A. Casadevall,, G. M. Cox,, and J. R. Perfect. 2001. Identification and characterization of the Cryptococcus neoformans phosphoisomannose isomerase-encoding gene, MAN1, and its impact on pathogenicity. Mol. Microbiol. 40: 610620.
149. Yoneda, A., and, T. L. Doering. 2006. A eukaryotic capsular polysaccharide is synthesized intracellularly and secreted via exocytosis. Mol. Biol. Cell 17: 51315140.
150. Yoneda, A., and, T. L. Doering. 2008. Regulation of Cryptococcus neoformans capsule size is mediated at the polymer level. Eukaryot. Cell 7: 546459.
151. Young, B. J., and, T. Kozel. 1993. Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect. Immun. 61: 29662972.
152. Zaragoza, O.,, B.C. Fries, and, A. Casadevall. 2003. Induction of capsule growth in Cryptococcus neoformans by mammalian serum and CO 2. Infect. Immun. 71: 61556164.


Generic image for table

The Cap proteins

Citation: Janbon G, Doering T. 2011. Biosynthesis and Genetics of the Capsule, p 27-41. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch3

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