Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway

Lee, I. Russel, Lui, Edmund Y. L., Chow, Eve W. L., Arras, Samantha D. M., Morrow, Carl A. and Fraser, James A. (2013) Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway. Genetics, 194 2: 421-U199. doi:10.1534/genetics.113.150326


Author Lee, I. Russel
Lui, Edmund Y. L.
Chow, Eve W. L.
Arras, Samantha D. M.
Morrow, Carl A.
Fraser, James A.
Title Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway
Formatted title
Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway
Journal name Genetics   Check publisher's open access policy
ISSN 0016-6731
Publication date 2013-06
Sub-type Article (original research)
DOI 10.1534/genetics.113.150326
Open Access Status
Volume 194
Issue 2
Start page 421
End page U199
Total pages 27
Place of publication Bethesda, MD, United States
Publisher Genetics Society of America
Collection year 2014
Language eng
Formatted abstract
Degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2Δ mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2Δ mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2Δ mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism.
Keyword Cryptococcus neoformans
Nitrogen
P5C dehydrogenase
Proline oxidase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 12 Jul 2013, 13:54:21 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences