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Proteomics of Rat Lungs Infected by Cryptococcus gattii Reveals a Potential Warburg-like Effect.
- Source :
-
Journal of proteome research [J Proteome Res] 2019 Nov 01; Vol. 18 (11), pp. 3885-3895. Date of Electronic Publication: 2019 Sep 26. - Publication Year :
- 2019
-
Abstract
- Cryptococcus gattii is the causative agent of cryptococcosis infection that can lead to pneumonia and meningitis in immunocompetent individuals. The molecular basis of the pathogenic process and impact on the host biochemistry are poorly understood and remain largely unknown. In this context, a comparative proteomic analysis was performed to investigate the response of the host during an infection caused by C. gattii . Lungs of experimentally infected rats were analyzed by shotgun proteomics to identify differentially expressed proteins induced by C. gattii clinical strain. The proteomic results were characterized using bioinformatic tools, and subsequently, the molecular findings were validated in cell culture and lungs of infected animals. A dramatic change was observed in protein expression triggered by C. gattii infection, especially related to energy metabolism. The main pathways affected include aerobic glycolysis cycle, TCA cycle, and pyrimidine and purine metabolism. Analyses in human lung fibroblast cells confirmed the altered metabolic status found in infected lungs. Thus, it is clear that C. gattii infection triggers important changes in energy metabolism leading to the activation of glycolysis and lactate accumulation in lung cells, culminating in a cancerlike metabolic status known as the Warburg effect. The results presented here provide important insights to better understand C. gattii molecular pathogenesis.
- Subjects :
- Animals
Cell Line
Cryptococcosis microbiology
Cryptococcus gattii physiology
Disease Models, Animal
Fibroblasts cytology
Fibroblasts metabolism
Fibroblasts microbiology
Host-Pathogen Interactions
Humans
Lung microbiology
Male
Rats, Wistar
Cryptococcosis metabolism
Energy Metabolism physiology
Glycolysis physiology
Lung metabolism
Proteome metabolism
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 18
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 31502459
- Full Text :
- https://doi.org/10.1021/acs.jproteome.9b00326