Skip to main content
SpringerLink
Log in

Polysaccharides of Fungal Origin

Focus on the Capsule of the Pathogen Cryptococcus neoformans

  • Living reference work entry
  • First Online:
Polysaccharides of Microbial Origin

  • 58 Accesses

Abstract

Cryptococcus neoformans was first isolated as a human pathogen in the 1890s. Subsequent study has shown that the polysaccharide capsule of C. neoformans is a key virulence factor. Unlike in bacteria, the pathways for fungal polysaccharide synthesis are not well characterized with only a single glycosytransferase – β-(1,2)-xylosyltranferase Cxt1 – having been confirmed. While there is evidence that polysaccharide synthesis occurs in the cytosol and is transported to the extracellular space in extracellular vesicles, how the capsule attaches to the cell and why some polymers are secreted instead of incorporated into the capsular architecture remains a mystery. In this chapter we explore this along with our current biophysical, structural, and immunological understanding of cryptococcal polysaccharides. From these studies we outline the outstanding questions in the field and identify a bevy of techniques and applications open for future research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  • Bacon BE, Cherniak R. Structure of the O-deacetylated glucuronoxylomannan from Cryptococcus neoformans serotype C as determined by 2D 1H NMR spectroscopy. Carbohydr Res. 1995;276(2):365–86.

    Article  CAS  PubMed  Google Scholar 

  • Bacon BE, Cherniak R, Kwon-Chung KJ, Jacobson ES. Structure of the O-deacetylated glucuronoxylomannan from Cryptococcus neoformans Cap70 as determined by 2D NMR spectroscopy. Carbohydr Res. 1996;283:95–110.

    Article  CAS  PubMed  Google Scholar 

  • Barnett JA. A history of research on yeasts 14: medical yeasts part 2, Cryptococcus neoformans. Yeast. 2010;27(11):875–904.

    Article  CAS  PubMed  Google Scholar 

  • Benham RW. The terminology of the Cryptococci with a note on Cryptococcus Mollis. Mycologia. 1935;27(5):496–502.

    Article  Google Scholar 

  • Bulmer GS, Sans MD. Cryptococcus neoformans. 3. Inhibition of phagocytosis. J Bacteriol. 1968;95(1):5–8.

    Google Scholar 

  • Burchard W. Light scattering from polysaccharides as soft materials. In: Borsali R, Pecora R, editors. Soft matter characterization. Dordrecht: Springer Netherlands; 2008. p. 463–603.

    Chapter  Google Scholar 

  • Casadevall A. Antibody-based therapies as anti-infective agents. Expert Opin Investig Drugs. 1998;7(3):307–21.

    Article  CAS  PubMed  Google Scholar 

  • Casadevall A, Scharff MD. The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding antibodies. J Exp Med. 1991;174(1):151–60.

    Article  CAS  PubMed  Google Scholar 

  • Casadevall A, Mukherjee J, Devi SJ, Schneerson R, Robbins JB, Scharff MD. Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection. J Infect Dis. 1992;165(6):1086–93.

    Article  CAS  PubMed  Google Scholar 

  • Casadevall A, Coelho C, Cordero RJB, Dragotakes Q, Jung E, Vij R, et al. The capsule of Cryptococcus neoformans. Virulence. 2019;10(1):822–31.

    Article  CAS  PubMed  Google Scholar 

  • Chang YC, Kwon-Chung KJ. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol. 1994;14(7):4912–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chang YC, Kwon-Chung KJ. Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans. Infect Immun. 1998;66(5):2230–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cherniak R, Sundstrom JB. Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect Immun. 1994;62(5):1507–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cherniak R, Jones RG, Reiss E. Structure determination of Cryptococcus neoformans serotype A-variant glucuronoxylomannan by 13C-n.m.r. spectroscopy. Carbohydr Res. 1988;172(1):113–38.

    Article  CAS  PubMed  Google Scholar 

  • Cherniak R, Valafar H, Morris LC, Valafar F. Cryptococcus neoformans chemotyping by quantitative analysis of 1H nuclear magnetic resonance spectra of glucuronoxylomannans with a computer-simulated artificial neural network. Clin Diagn Lab Immunol. 1998;5(2):146–59.

    Google Scholar 

  • Cleare W, Casadevall A. Scanning electron microscopy of encapsulated and non-encapsulated Cryptococcus neoformans and the effect of glucose on capsular polysaccharide release. Med Mycol. 1999;37(4):235–43.

    CAS  PubMed  Google Scholar 

  • Cordero RJB, Frases S, Guimaräes AJ, Rivera J, Casadevall A. Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity. Mol Microbiol. 2011;79(4):1101–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crawford C, Cordero RJB, Guazzelli L, Wear MP, Oscarson S, Casadevall A. Exploring Cryptococcus neoformans capsule structure and assembly with a hydroxylamine-armed fluorescent probe. BioRxiv. 2019.

    Google Scholar 

  • Cuthbertson L, Mainprize IL, Naismith JH, Whitfield C. Pivotal roles of the outer membrane polysaccharide export and polysaccharide copolymerase protein families in export of extracellular polysaccharides in gram-negative bacteria. Microbiol Mol Biol Rev. 2009;73(1):155–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de S Araújo GR, Viana NB, Pontes B, Frases S. Rheological properties of cryptococcal polysaccharide change with fiber size, antibody binding and temperature. Future Microbiol. 2019;14:867–84.

    Article  PubMed  Google Scholar 

  • Devi SJ. Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. Vaccine. 1996;14(9):841–4.

    Article  CAS  PubMed  Google Scholar 

  • Devi SJ, Schneerson R, Egan W, Ulrich TJ, Bryla D, Robbins JB, et al. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity. Infect Immun. 1991;59(10):3700–7.

    Google Scholar 

  • Dromer F, Salamero J, Contrepois A, Carbon C, Yeni P. Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide. Infect Immun. 1987a;55(3):742–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dromer F, Charreire J, Contrepois A, Carbon C, Yeni P. Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun. 1987b;55(3):749–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drouhet E, Segretain G, Aubert JP. Capsular polyoxide of a pathogenic fungus, Torulopsis neoformans. Relation with virulence. Ann Inst Pasteur. 1950.

    Google Scholar 

  • Eckert TF, Kozel TR. Production and characterization of monoclonal antibodies specific for Cryptococcus neoformans capsular polysaccharide. Infect Immun. 1987;55(8):1895–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edwards MR, Gordon MA, Lapa EW, Ghiorse WC. Micromorphology of Cryptococcus neoformans. J Bacteriol. 1967;94(3):766–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frases S, Nimrichter L, Viana NB, Nakouzi A, Casadevall A. Cryptococcus neoformans capsular polysaccharide and exopolysaccharide fractions manifest physical, chemical, and antigenic differences. Eukaryot Cell. 2008;7(2):319–27.

    Google Scholar 

  • Frases S, Pontes B, Nimrichter L, Viana NB, Rodrigues ML, Casadevall A. Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules. Proc Natl Acad Sci U S A. 2009;106(4):1228–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frases S, Viana NB, Casadevall A. Biophysical methods for the study of microbial surfaces. Front Microbiol. 2011;2:207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freeze HH, Elbein AD. Glycosylation precursors. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, et al., editors. Essentials of glycobiology. 2nd ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2009.

    Google Scholar 

  • Gladebusch H. Active immunization against Cryptococcus neoformans on JSTOR [Internet]. 1958 [cited 2020 Jun 29]. Available from: https://www-jstor-org.proxy1.library.jhu.edu/stable/30098404#metadata_info_tab_contents

  • Guazzelli L, Ulc R, Bowen A, Crawford C, McCabe O, Jedlicka AJ, et al. A synthetic glycan array containing Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide fragments allows the mapping of protective epitopes. 2020.

    Google Scholar 

  • Klutts JS, Doering TL. Cryptococcal xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans plays a direct role in the synthesis of capsule polysaccharides. J Biol Chem. 2008;283(21):14327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klutts JS, Levery SB, Doering TL. A beta-1,2-xylosyltransferase from Cryptococcus neoformans defines a new family of glycosyltransferases. J Biol Chem. 2007;282(24):17890–9.

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Heiss C, Santiago-Tirado FH, Black I, Azadi P, Doering TL. Pbx proteins in Cryptococcus neoformans cell wall remodeling and capsule assembly. Eukaryot Cell. 2014;13(5):560–71.

    Article  PubMed  PubMed Central  Google Scholar 

  • Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A, Cloud GA, et al. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother. 2005;49(3):952–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lombard V, Golaconda Ramulu H, Drula E, Coutinho PM, Henrissat B. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 2014;42(Database issue):D490–5.

    Article  CAS  PubMed  Google Scholar 

  • Maxson ME, Cook E, Casadevall A, Zaragoza O. The volume and hydration of the Cryptococcus neoformans polysaccharide capsule. Fungal Genet Biol. 2007a;44(3):180–6.

    Article  CAS  PubMed  Google Scholar 

  • Maxson ME, Dadachova E, Casadevall A, Zaragoza O. Radial mass density, charge, and epitope distribution in the Cryptococcus neoformans capsule. Eukaryot Cell. 2007b;6(1):95–109.

    Article  CAS  PubMed  Google Scholar 

  • McClelland EE, Bernhardt P, Casadevall A. Estimating the relative contributions of virulence factors for pathogenic microbes. Infect Immun. 2006;74(3):1500–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McFadden D, Zaragoza O, Casadevall A. The capsular dynamics of Cryptococcus neoformans. Trends Microbiol. 2006a;14(11):497–505.

    Article  CAS  PubMed  Google Scholar 

  • McFadden DC, De Jesus M, Casadevall A. The physical properties of the capsular polysaccharides from Cryptococcus neoformans suggest features for capsule construction. J Biol Chem. 2006b;281(4):1868–75.

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee J, Casadevall A, Scharff MD. Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization. J Exp Med. 1993;177(4):1105–16.

    Article  CAS  PubMed  Google Scholar 

  • Nakouzi A, Zhang T, Oscarson S, Casadevall A. The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies. Vaccine. 2009;27(27):3513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nimrichter L, Frases S, Cinelli LP, Viana NB, Nakouzi A, Travassos LR, et al. Self-aggregation of Cryptococcus neoformans capsular glucuronoxylomannan is dependent on divalent cations. Eukaryot Cell. 2007;6(8):1400–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oliveira DL, Nimrichter L, Miranda K, Frases S, Faull KF, Casadevall A, et al. Cryptococcus neoformans cryoultramicrotomy and vesicle fractionation reveals an intimate association between membrane lipids and glucuronoxylomannan. Fungal Genet Biol. 2009;46(12):956–63.

    Google Scholar 

  • Oscarson S, Alpe M, Svahnberg P, Nakouzi A, Casadevall A. Synthesis and immunological studies of glycoconjugates of Cryptococcus neoformans capsular glucuronoxylomannan oligosaccharide structures. Vaccine. 2005;23(30):3961–72.

    Article  CAS  PubMed  Google Scholar 

  • Pontes B, Frases S. The Cryptococcus neoformans capsule: lessons from the use of optical tweezers and other biophysical tools. Front Microbiol. 2015;6:640.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ramos CL, Gomes FM, Girard-Dias W, Almeida FP, Albuquerque PC, Kretschmer M, et al. Phosphorus-rich structures and capsular architecture in Cryptococcus neoformans. Future Microbiol. 2017;12:227–38.

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues ML, Nimrichter L, Oliveira DL, Frases S, Miranda K, Zaragoza O, et al. Vesicular polysaccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport. Eukaryot Cell. 2007;6(1):48–59.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi N. Ultrastructural study of hepatic granulomas induced by Cryptococcus neoformans by quick-freezing and deep-etching method. Virchows Archiv B Cell Pathol. 1993;64(1):57–66.

    Article  CAS  Google Scholar 

  • Sakaguchi N, Baba T, Fukuzawa M, Ohno S. Ultrastructural study of Cryptococcus neoformans by quick-freezing and deep-etching method. Mycopathologia. 1993;121(3):133–41.

    Article  CAS  PubMed  Google Scholar 

  • Sande C, Bouwman C, Kell E, Nickerson NN, Kapadia SB, Whitfield C. Structural and functional variation in outer membrane polysaccharide export (OPX) proteins from the two major capsule assembly pathways present in Escherichia coli. J Bacteriol. 2019;201(14):e00213–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng S, Cherniak R. Structure of the 13C-enriched O-deacetylated glucuronoxylomannan of Cryptococcus neoformans serotype A determined by NMR spectroscopy. Carbohydr Res. 1997;301(1–2):33–40.

    Article  CAS  PubMed  Google Scholar 

  • Sheridan C. Convalescent serum lines up as first-choice treatment for coronavirus. Nat Biotechnol. 2020;38(6):655–8.

    Article  CAS  PubMed  Google Scholar 

  • Skelton MA, Cherniak R, Poppe L, van Halbeek H. Structure of the De-O-acetylated glucuronoxylomannan from Cryptococcus neoformans serotype D, as determined by 2D NMR spectroscopy. Magn Reson Chem. 1991;29(8):786–93.

    Article  Google Scholar 

  • Takeo K, Uesaka I, Uehira K, Nishiura M. Fine structure of Cryptococcus neoformans grown in vitro as observed by freeze-etching. J Bacteriol. 1973;113(3):1442–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tassieri M, Del Giudice F, Robertson EJ, Jain N, Fries B, Wilson R, et al. Microrheology with optical tweezers: measuring the relative viscosity of solutions “at a glance”. Sci Rep. 2015;5:8831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turner SH, Cherniak R. Glucuronoxylomannan of Cryptococcus neoformans serotype B: structural analysis by gas-liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. Carbohydr Res. 1991;211(1):103–16.

    Article  CAS  PubMed  Google Scholar 

  • Turner SH, Cherniak R, Reiss E, Kwon-Chung KJ. Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy. Carbohydr Res. 1992;233:205–18.

    Article  CAS  PubMed  Google Scholar 

  • Vaishnav VV, Bacon BE, O’Neill M, Cherniak R. Structural characterization of the galactoxylomannan of Cryptococcus neoformans Cap67. Carbohydr Res. 1998;306(1–2):315–30.

    Article  CAS  PubMed  Google Scholar 

  • Walter JE, Coffee EG. Distribution and epidemiologic significance of the serotypes of Cryptococcus neoformans. Am J Epidemiol. 1968;87(1):167–72.

    Article  CAS  PubMed  Google Scholar 

  • Wang ZA, Li LX, Doering TL. Unraveling synthesis of the cryptococcal cell wall and capsule. Glycobiology. 2018;28(10):719–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei M, McKitrick TR, Mehta AY, Gao C, Jia N, McQuillan AM, et al. Novel reversible fluorescent glycan linker for functional glycomics. Bioconjug Chem. 2019;30(11):2897–908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitfield C. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu Rev Biochem. 2006;75:39–68.

    Article  CAS  PubMed  Google Scholar 

  • Willis LM, Whitfield C. Structure, biosynthesis, and function of bacterial capsular polysaccharides synthesized by ABC transporter-dependent pathways. Carbohydr Res. 2013;378:35–44.

    Article  CAS  PubMed  Google Scholar 

  • Wilson DE, Bennett JE, Bailey JW. Serologic grouping of Cryptococcus neoformans. Proc Soc Exp Biol Med. 1968;127(3):820–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Maggie P. Wear & Arturo Casadevall

Authors
  1. Maggie P. Wear
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arturo Casadevall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maggie P. Wear .

Editor information

Editors and Affiliations

  1. 3Bs Research Grp, Zona Indus da Gan, University of Minho, BARCO GMR, Portugal

    Joaquim Oliveira

  2. 3Bs Research Grp, Zona Indus da Gan, University of Minho, BARCO GMR, Portugal

    Hajer Radhouani

  3. 3Bs Research Grp, Zona Indus da Gan, University of Minho, BARCO GMR, Portugal

    Rui L. Reis

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Wear, M.P., Casadevall, A. (2021). Polysaccharides of Fungal Origin. In: Oliveira, J., Radhouani, H., Reis, R.L. (eds) Polysaccharides of Microbial Origin. Springer, Cham. https://doi.org/10.1007/978-3-030-35734-4_29-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-35734-4_29-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-35734-4

  • Online ISBN: 978-3-030-35734-4

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation