PDF(Pubmed)
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.
摘要：
副角菌病复合体的成员是副角菌病（PCM）的病原体，一种拉丁美洲特有的人类全身性真菌病。在与主机初步联系后，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。适应营养胁迫是真菌在宿主组织中的关键特征。真菌通过氮代谢物抑制(NCR)利用氮源。NCR确保清除，替代氮源的吸收和分解代谢，当优惠的时候，如谷氨酰胺或铵，不可用。NanoUPLC-MSE蛋白质组学方法用于研究在脯氨酸或谷氨酰胺作为氮源生长后的Lutzzi副球菌的NCR反应。鉴定了总共338种差异表达的蛋白质。卢茨疟原虫证明了糖异生，β-氧化，乙醛酸循环，粘附素样蛋白质，在NCR-脯氨酸条件下引发应激反应和细胞壁重塑。此外,在巨噬细胞内，在NCR-脯氨酸条件下训练的酵母细胞显示出增强的生存能力。总的来说,这项研究可以全面了解真菌克服营养饥饿的NCR反应，在人体宿主中表现为营养免疫。反过来,病原体需要快速适应巨噬细胞诱导的不断变化的微环境才能成功感染。
