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Published on: March 13, 2014
Proteomics of Paracoccidioides lutzii: Overview of Changes Triggered by Nitrogen Catabolite Repression
Vanessa Rafaela Milhomem Cruz-Leite1, André Luís Elias Moreira1, Lana O'Hara Souza Silva1
1Department of Biochemistry and Molecular Biology, Institute of Biological Sciences II, Federal University of Goiás, Goiânia 74690-900, GO, Brazil.
Abstract:
Members of the Paracoccidioides complex are the causative agents of Paracoccidioidomycosis (PCM), a human systemic mycosis endemic in Latin America. Upon initial contact with the host, the pathogen needs to uptake micronutrients. Nitrogen is an essential source for biosynthetic pathways. Adaptation to nutritional stress is a key feature of fungi in host tissues. Fungi utilize nitrogen sources through Nitrogen Catabolite Repression (NCR). NCR ensures the scavenging, uptake and catabolism of alternative nitrogen sources, when preferential ones, such as glutamine or ammonium, are unavailable. The NanoUPLC-MSE proteomic approach was used to investigate the NCR response of Paracoccidioides lutzii after growth on proline or glutamine as a nitrogen source. A total of 338 differentially expressed proteins were identified. P. lutzii demonstrated that gluconeogenesis, β-oxidation, glyoxylate cycle, adhesin-like proteins, stress response and cell wall remodeling were triggered in NCR-proline conditions. In addition, within macrophages, yeast cells trained under NCR-proline conditions showed an increased ability to survive. In general, this study allows a comprehensive understanding of the NCR response employed by the fungus to overcome nutritional starvation, which in the human host is represented by nutritional immunity. In turn, the pathogen requires rapid adaptation to the changing microenvironment induced by macrophages to achieve successful infection.
Insights
Paracoccidioides lutzii adapts to host nitrogen scarcity by activating specific metabolic pathways under Nitrogen Catabolite Repression (NCR). This adaptation enhances fungal survival within macrophages, crucial for overcoming host nutritional immunity during infection.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides complex, endemic in Latin America.
- Fungal adaptation to host nutritional stress, particularly nitrogen availability, is critical for infection.
- Nitrogen Catabolite Repression (NCR) regulates fungal nitrogen source utilization.
Purpose of the Study:
- To investigate the proteomic changes in Paracoccidioides lutzii under Nitrogen Catabolite Repression (NCR) conditions.
- To understand how P. lutzii adapts to proline as an alternative nitrogen source.
- To assess the impact of NCR-mediated adaptation on fungal survival within macrophages.
Main Methods:
- NanoUPLC-MS^E proteomic analysis was employed to compare P. lutzii grown on proline versus glutamine.
- Differential protein expression was quantified to identify key adaptive responses.
- Yeast survival assays within macrophages were performed for trained and untrained cells.
Main Results:
- A total of 338 differentially expressed proteins were identified between NCR-proline and NCR-glutamine conditions.
- Growth on proline induced gluconeogenesis, beta-oxidation, the glyoxylate cycle, stress response, and cell wall remodeling.
- Yeast cells pre-conditioned under NCR-proline conditions exhibited enhanced survival within macrophages.
Conclusions:
- P. lutzii activates specific metabolic and cellular processes to cope with nitrogen starvation, a key feature of host nutritional immunity.
- Adaptation to alternative nitrogen sources like proline enhances fungal virulence and survival in the macrophage environment.
- Understanding NCR in P. lutzii provides insights into fungal pathogenesis and host-pathogen interactions.
