ArticleGenetics2013
Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway.
Article in Genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Puf4 -mediated oxidative stress virulence attenuation inFrontiers in cellular and infection microbiology · 2025Article
- Research progress on the function and regulatory pathways of amino acid permeases in fungi.World journal of microbiology & biotechnology · 2024Review
- Proline catabolism is a key factor facilitating Candida albicans pathogenicity.PLoS pathogens · 2023Article
- Resolving the Temporal Splenic Proteome during Fungal Infection for Discovery of Putative Dual Perspective Biomarker Signatures.Journal of the American Society for Mass Spectrometry · 2023Article
- Article
- In vitro anti-Cryptococcus activity of diphenyl diselenide alone and in combination with amphotericin B and fluconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- GATA-type transcription factors play a vital role in radiation sensitivity of Cryptococcus neoformans by regulating the gene expression of specific amino acid permeases.Scientific reports · 2019Article
- Role of Proline in Pathogen and Host Interactions.Antioxidants & redox signaling · 2019Review
- Structural Biology of Proline Catabolic Enzymes.Antioxidants & redox signaling · 2019Review
- Enhanced synthesis of poly gamma glutamic acid by increasing the intracellular reactive oxygen species in the Bacillus licheniformis Δ1-pyrroline-5-carboxylate dehydrogenase gene ycgN-deficient strain.Applied microbiology and biotechnology · 2018Article
- Biological Roles of Ornithine Aminotransferase (OAT) in Plant Stress Tolerance: Present Progress and Future Perspectives.International journal of molecular sciences · 2018Review
- Article
- Redox Modulation of Oligomeric State in Proline Utilization A.Biophysical journal · 2018Article
- Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi.Molecular microbiology · 2018Review
- Article
- Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure.The FEBS journal · 2017Article
- Engineering a trifunctional proline utilization A chimaera by fusing a DNA-binding domain to a bifunctional PutA.Bioscience reports · 2016Article
- Role of Δ1-pyrroline-5-carboxylate dehydrogenase supports mitochondrial metabolism and host-cell invasion of Trypanosoma cruzi.The Journal of biological chemistry · 2015Article
- Role of proline and pyrroline-5-carboxylate metabolism in plant defense against invading pathogens.Frontiers in plant science · 2015Review
- Structures of the PutA peripheral membrane flavoenzyme reveal a dynamic substrate-channeling tunnel and the quinone-binding site.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 Δ(1)-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.