Posttranslational, translational, and transcriptional responses to nitric oxide stress in Cryptococcus neoformans: implications for virulence. Eukaryot Cell 2006 Mar;5(3):518-29
Date
03/10/2006Pubmed ID
16524907Pubmed Central ID
PMC1398057DOI
10.1128/EC.5.3.518-529.2006Scopus ID
2-s2.0-33645054564 (requires institutional sign-in at Scopus site) 71 CitationsAbstract
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 glr1Delta 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.
Author List
Missall TA, Pusateri ME, Donlin MJ, Chambers KT, Corbett JA, Lodge JKAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Aconitate HydrataseAnimals
Cryptococcus neoformans
Dose-Response Relationship, Drug
Female
Gene Expression Regulation, Fungal
Genes, Fungal
Genomics
Mice
Mice, Inbred CBA
Nitric Oxide
Oxidative Stress
Peroxidases
Protein Processing, Post-Translational
Proteomics
Transaldolase
Transcription, Genetic
Virulence
