Cruz-Leite Vanessa Rafaela Milhomem, Moreira André Luís Elias, Silva Lana O'Hara Souza, Inácio Moises Morais, Parente-Rocha Juliana Alves, Ruiz Orville Hernandez, Weber Simone Schneider, Soares Célia Maria de Almeida, Borges Clayton Luiz
Department of Biochemistry and Molecular Biology, Institute of Biological Sciences II, Federal University of Goiás, Goiânia 74690-900, GO, Brazil.
Estácio de Goiás University Center-FESGO, Goiânia 74063-010, GO, Brazil.
J Fungi (Basel). 2023 Nov 12;9(11):1102. doi: 10.3390/jof9111102.
Members of the 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-MS proteomic approach was used to investigate the NCR response of after growth on proline or glutamine as a nitrogen source. A total of 338 differentially expressed proteins were identified. 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.
该复合体的成员是副球孢子菌病（PCM）的病原体，PCM是一种在拉丁美洲流行的人类全身性真菌病。在初次与宿主接触时，病原体需要摄取微量营养素。氮是生物合成途径的重要来源。适应营养应激是真菌在宿主组织中的一个关键特征。真菌通过氮代谢物阻遏（NCR）利用氮源。当优先的氮源（如谷氨酰胺或铵）不可用时，NCR确保替代氮源的清除、摄取和分解代谢。采用纳升级超高效液相色谱-质谱蛋白质组学方法研究了在以脯氨酸或谷氨酰胺作为氮源生长后该菌的NCR反应。共鉴定出338种差异表达蛋白。结果表明，在NCR-脯氨酸条件下，糖异生、β-氧化、乙醛酸循环、黏附素样蛋白、应激反应和细胞壁重塑被触发。此外，在巨噬细胞内，在NCR-脯氨酸条件下训练的酵母细胞存活能力增强。总的来说，这项研究有助于全面了解该真菌用于克服营养饥饿的NCR反应，在人类宿主中营养饥饿表现为营养免疫。反过来，病原体需要迅速适应巨噬细胞诱导的不断变化的微环境以实现成功感染。
