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Eukaryotic Cell, March 2006, p. 518-529, Vol. 5, No. 3
1535-9778/06/$08.00+0     doi:10.1128/EC.5.3.518-529.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Posttranslational, Translational, and Transcriptional Responses to Nitric Oxide Stress in Cryptococcus neoformans: Implications for Virulence{dagger}

Tricia A. Missall,1 Mary Ellen Pusateri,1 Maureen J. Donlin,1,2 Kari T. Chambers,1 John A. Corbett,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, St. Louis, Missouri 631042

Received 28 June 2005/ Accepted 26 December 2005

The ability of the fungal pathogen Cryptococcus neoformans to evade the mammalian innate immune response and cause disease is partially due to its ability to respond to and survive nitrosative stress. In this study, we use proteomic and genomic approaches to elucidate the response of C. neoformans to nitric oxide stress. This nitrosative stress response involves both transcriptional, translational, and posttranslational regulation. Proteomic and genomic analyses reveal changes in expression of stress response genes. In addition, genes involved in cell wall organization, respiration, signal transduction, transport, transcriptional control, and metabolism show altered expression under nitrosative conditions. Posttranslational modifications of transaldolase (Tal1), aconitase (Aco1), and the thiol peroxidase, Tsa1, are regulated during nitrosative stress. One stress-related protein up-regulated in the presence of nitric oxide stress is glutathione reductase (Glr1). To further investigate its functional role during nitrosative stress, a deletion mutant was generated. We show that this glr1{Delta} mutant is sensitive to nitrosative stress and macrophage killing in addition to being avirulent in mice. These studies define the response to nitrosative stress in this important fungal pathogen.


* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104. Phone: (314) 977-9217. Fax: (314) 977-9205. E-mail: lodgejk{at}slu.edu.

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


Eukaryotic Cell, March 2006, p. 518-529, Vol. 5, No. 3
1535-9778/06/$08.00+0     doi:10.1128/EC.5.3.518-529.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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