Vesicular Polysaccharide Export in Cryptococcus Neoformans is a Eukaryotic Solution to the Problem of Fungal Trans-cell Wall Transport

Overview

Journal Eukaryot Cell

Publisher American Society for Microbiology

Specialty Molecular Biology

Date 2006 Nov 23

PMID 17114598

Citations 279

Authors

Marcio L Rodrigues

Leonardo Nimrichter

Debora L Oliveira

Susana Frases

Kildare Miranda

Oscar Zaragoza

Mauricio Alvarez

Antonio Nakouzi

Marta Feldmesser

Arturo Casadevall

Affiliations

Soon will be listed here.

Abstract

The mechanisms by which macromolecules are transported through the cell wall of fungi are not known. A central question in the biology of Cryptococcus neoformans, the causative agent of cryptococcosis, is the mechanism by which capsular polysaccharide synthesized inside the cell is exported to the extracellular environment for capsule assembly and release. We demonstrate that C. neoformans produces extracellular vesicles during in vitro growth and animal infection. Vesicular compartments, which are transferred to the extracellular space by cell wall passage, contain glucuronoxylomannan (GXM), a component of the cryptococcal capsule, and key lipids, such as glucosylceramide and sterols. A correlation between GXM-containing vesicles and capsule expression was observed. The results imply a novel mechanism for the release of the major virulence factor of C. neoformans whereby polysaccharide packaged in lipid vesicles crosses the cell wall and the capsule network to reach the extracellular environment.

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References

Casadevall A, Mukherjee J, Scharff M . Monoclonal antibody based ELISAs for cryptococcal polysaccharide. J Immunol Methods. 1992; 154(1):27-35. DOI: 10.1016/0022-1759(92)90209-c. View

Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Gast D, Joumaa S . ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles. FASEB J. 2002; 17(2):292-4. DOI: 10.1096/fj.02-0430fje. View

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. DOI: 10.1007/BF01104068. View

Mare L, Iatta R, Montagna M, Luberto C, Del Poeta M . APP1 transcription is regulated by inositol-phosphorylceramide synthase 1-diacylglycerol pathway and is controlled by ATF2 transcription factor in Cryptococcus neoformans. J Biol Chem. 2005; 280(43):36055-64. DOI: 10.1074/jbc.M507285200. View

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. 1987; 55(3):742-8. PMC: 260404. DOI: 10.1128/iai.55.3.742-748.1987. View

Heung L, Luberto C, Plowden A, Hannun Y, Del Poeta M . The sphingolipid pathway regulates Pkc1 through the formation of diacylglycerol in Cryptococcus neoformans. J Biol Chem. 2004; 279(20):21144-53. DOI: 10.1074/jbc.M312995200. View

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. DOI: 10.1016/j.vaccine.2005.02.029. View

NOVIKOFF A, Novikoff P . Cytochemical contributions to differentiating GERL from the Golgi apparatus. Histochem J. 1977; 9(5):525-51. DOI: 10.1007/BF01002901. View

Takeo K, UESAKA I, Uehira K, Nishiura M . Fine structure of Cryptococcus neoformans grown in vivo as observed by freeze-etching. J Bacteriol. 1973; 113(3):1449-54. PMC: 251716. DOI: 10.1128/jb.113.3.1449-1454.1973. View

10.

Garcia-Rivera J, Chang Y, Kwon-Chung K, Casadevall A . Cryptococcus neoformans CAP59 (or Cap59p) is involved in the extracellular trafficking of capsular glucuronoxylomannan. Eukaryot Cell. 2004; 3(2):385-92. PMC: 387637. DOI: 10.1128/EC.3.2.385-392.2004. View

11.

Rodrigues M, Travassos L, Miranda K, Franzen A, Rozental S, De Souza W . Human antibodies against a purified glucosylceramide from Cryptococcus neoformans inhibit cell budding and fungal growth. Infect Immun. 2000; 68(12):7049-60. PMC: 97815. DOI: 10.1128/IAI.68.12.7049-7060.2000. View

12.

Vecchiarelli A . Immunoregulation by capsular components of Cryptococcus neoformans. Med Mycol. 2001; 38(6):407-17. DOI: 10.1080/mmy.38.6.407.417. View

13.

Nimrichter L, Cerqueira M, Leitao E, Miranda K, Nakayasu E, Almeida S . Structure, cellular distribution, antigenicity, and biological functions of Fonsecaea pedrosoi ceramide monohexosides. Infect Immun. 2005; 73(12):7860-8. PMC: 1307093. DOI: 10.1128/IAI.73.12.7860-7868.2005. View

14.

Feldmesser M, Casadevall A, Kress Y, Spira G, Orlofsky A . Eosinophil-Cryptococcus neoformans interactions in vivo and in vitro. Infect Immun. 1997; 65(5):1899-907. PMC: 175238. DOI: 10.1128/iai.65.5.1899-1907.1997. View

15.

Chang Y, Kwon-Chung K . Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol. 1994; 14(7):4912-9. PMC: 358863. DOI: 10.1128/mcb.14.7.4912-4919.1994. View

16.

Muniz M, Riezman H . Intracellular transport of GPI-anchored proteins. EMBO J. 2000; 19(1):10-5. PMC: 1171772. DOI: 10.1093/emboj/19.1.10. View

17.

Tucker S, Casadevall A . Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm. Proc Natl Acad Sci U S A. 2002; 99(5):3165-70. PMC: 122490. DOI: 10.1073/pnas.052702799. View

18.

de Souza Pereira R, Geibel J . Direct observation of oxidative stress on the cell wall of Saccharomyces cerevisiae strains with atomic force microscopy. Mol Cell Biochem. 2000; 201(1-2):17-24. DOI: 10.1023/a:1007007704657. View

19.

Zaragoza O, Casadevall A . Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online. 2004; 6:10-15. PMC: 389900. DOI: 10.1251/bpo68. View

20.

Feldmesser M, Kress Y, Novikoff P, Casadevall A . Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection. Infect Immun. 2000; 68(7):4225-37. PMC: 101732. DOI: 10.1128/IAI.68.7.4225-4237.2000. View