Institute of Biological Sciences and Technology, Guangxi Academy of Sciences, Nanning, Guangxi, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Appl Environ Microbiol. 2024 Sep 18;90(9):e0113824. doi: 10.1128/aem.01138-24. Epub 2024 Aug 19.
Phosphoglucose isomerase (PGI) links glycolysis, the pentose phosphate pathway (PPP), and the synthesis of cell wall precursors in fungi by facilitating the reversible conversion between glucose-6-phosphate (Glc6p) and fructose-6-phosphate (Fru6P). In a previous study, we established the essential role of PGI in cell wall biosynthesis in the opportunistic human fungal pathogen , highlighting its potential as a therapeutic target. In this study, we conducted transcriptomic analysis and discovered that the Δ mutant exhibited enhanced glycolysis, reduced PPP, and an upregulation of cell wall precursor biosynthesis pathways. Phenotypic analysis revealed defective protein -glycosylation in the mutant, notably the absence of glycosylated virulence factors DPP V and catalase 1. Interestingly, the cell wall defects in the mutant were not accompanied by activation of the MpkA-dependent cell wall integrity (CWI) signaling pathway. Instead, nitrate assimilation was activated in the Δ mutant, stimulating glutamine synthesis and providing amino donors for chitin precursor biosynthesis. Blocking the nitrate assimilation pathway severely impaired the growth of the Δ mutant, highlighting the crucial role of nitrate assimilation in rescuing cell wall defects. This study unveils the connection between nitrogen assimilation and cell wall compensation in .IMPORTANCE is a common and serious human fungal pathogen that causes a variety of diseases. Given the limited availability of antifungal drugs and increasing drug resistance, it is imperative to understand the fungus' survival mechanisms for effective control of fungal infections. Our previous study highlighted the essential role of PGI in maintaining cell wall integrity, phosphate sugar homeostasis, and virulence. The present study further illuminates the involvement of PGI in protein -glycosylation. Furthermore, this research reveals that the nitrogen assimilation pathway, rather than the canonical MpkA-dependent CWI pathway, compensates for cell wall deficiencies in the mutant. These findings offer valuable insights into a novel adaptation mechanism of to address cell wall defects, which could hold promise for the treatment of infections.
磷酸葡萄糖异构酶（PGI）通过促进葡萄糖-6-磷酸（Glc6p）和果糖-6-磷酸（Fru6P）之间的可逆转化，将糖酵解、戊糖磷酸途径（PPP）和细胞壁前体的合成联系在一起，在真菌中。在之前的研究中，我们确立了 PGI 在机会性人类真菌病原体细胞壁生物合成中的重要作用，突出了其作为治疗靶点的潜力。在这项研究中，我们进行了转录组分析，发现Δ突变体表现出增强的糖酵解、减少的 PPP 和细胞壁前体生物合成途径的上调。表型分析显示突变体中的蛋白质糖基化缺陷，特别是缺乏糖基化的毒力因子 DPP V 和过氧化氢酶 1。有趣的是，突变体中的细胞壁缺陷没有伴随着 MpkA 依赖的细胞壁完整性（CWI）信号通路的激活。相反，硝酸盐同化在Δ突变体中被激活，刺激谷氨酰胺合成并为几丁质前体生物合成提供氨基供体。阻断硝酸盐同化途径严重损害了Δ突变体的生长，突出了硝酸盐同化在挽救细胞壁缺陷中的关键作用。这项研究揭示了氮同化与 中细胞壁补偿之间的联系。是一种常见且严重的人类真菌病原体，可引起多种疾病。鉴于抗真菌药物的有限可用性和不断增加的耐药性，了解真菌的生存机制对于有效控制真菌感染至关重要。我们之前的研究强调了 PGI 在维持细胞壁完整性、磷酸糖稳态和毒力中的重要作用。本研究进一步阐明了 PGI 在蛋白质糖基化中的作用。此外，这项研究表明，氮同化途径而不是经典的 MpkA 依赖的 CWI 途径，补偿了突变体中的细胞壁缺陷。这些发现为 应对细胞壁缺陷的新型适应机制提供了有价值的见解，这可能为感染的治疗提供了希望。
