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Eukaryotic Cell, May 2007, p. 855-867, Vol. 6, No. 5
1535-9778/07/$08.00+0     doi:10.1128/EC.00399-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Chitosan, the Deacetylated Form of Chitin, Is Necessary for Cell Wall Integrity in Cryptococcus neoformans{triangledown} ,{dagger}

Lorina G. Baker,1 Charles A. Specht,3 Maureen J. Donlin,1,2 and Jennifer K. Lodge1,2*

Edward A. Doisy Department of Biochemistry and Molecular Biology,1 Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, Saint Louis, Missouri 63104,2 Department of Medicine, University of Massachusetts, 364 Plantation Street, Worcester, Massachusetts 016053

Received 13 December 2006/ Accepted 18 March 2007

Cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococcal meningoencephalitis, particularly in immunocompromised patients. The fungal cell wall is an excellent target for antifungal therapies as it is an essential organelle that provides cell structure and integrity, it is needed for the localization or attachment of known virulence factors, including the polysaccharide capsule, melanin, and phospholipase, and it is critical for host-pathogen interactions. In C. neoformans, chitosan produced by the enzymatic removal of acetyl groups from nascent chitin polymers has been implicated as an important component of the vegetative cell wall. In this study, we identify four putative chitin/polysaccharide deacetylases in C. neoformans. We have demonstrated that three of these deacetylases, Cda1, Cda2, and Cda3, can account for all of the chitosan produced during vegetative growth in culture, but the function for one, Fpd1, remains undetermined. The data suggest a model for chitosan production in vegetatively growing C. neoformans where the three chitin deacetylases convert chitin generated by the chitin synthase Chs3 into chitosan. Utilizing a collection of chitin/polysaccharide deacetylase deletion strains, we determined that during vegetative growth, chitosan helps to maintain cell integrity and aids in bud separation. Additionally, chitosan is necessary for maintaining normal capsule width and the lack of chitosan results in a "leaky melanin" phenotype. Our analysis indicates that chitin deacetylases and the chitosan made by them may prove to be excellent antifungal targets.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104. Phone: (314) 977-9217. Fax: (314) 977-9205. E-mail: lodgejk{at}slu.edu

{triangledown} Published ahead of print on 30 March 2007.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, May 2007, p. 855-867, Vol. 6, No. 5
1535-9778/07/$08.00+0     doi:10.1128/EC.00399-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baker, L. G., Specht, C. A., Lodge, J. K. (2009). Chitinases Are Essential for Sexual Development but Not Vegetative Growth in Cryptococcus neoformans. Eukaryot Cell 8: 1692-1705 [Abstract] [Full Text]  
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