Silao Fitz Gerald S, Ljungdahl Per O
Department of Molecular Biosciences, Wenner-Gren Institute, SciLifeLab, Stockholm University, 114 19 Stockholm, Sweden.
Pathogens. 2021 Dec 22;11(1):5. doi: 10.3390/pathogens11010005.
Nutrient uptake is essential for cellular life and the capacity to perceive extracellular nutrients is critical for coordinating their uptake and metabolism. Commensal fungal pathogens, e.g., , have evolved in close association with human hosts and are well-adapted to using diverse nutrients found in discrete host niches. Human cells that cannot synthesize all amino acids require the uptake of the "essential amino acids" to remain viable. Consistently, high levels of amino acids circulate in the blood. Host proteins are rich sources of amino acids but their use depends on proteases to cleave them into smaller peptides and free amino acids. responds to extracellular amino acids by pleiotropically enhancing their uptake and derive energy from their catabolism to power opportunistic virulent growth. Studies using have established paradigms to understand metabolic processes in ; however, fundamental differences exist. The advent of CRISPR/Cas9-based methods facilitate genetic analysis in , and state-of-the-art molecular biological techniques are being applied to directly examine growth requirements in vivo and in situ in infected hosts. The combination of divergent approaches can illuminate the biological roles of individual cellular components. Here we discuss recent findings regarding nutrient sensing with a focus on amino acid uptake and metabolism, processes that underlie the virulence of .
营养物质摄取对于细胞生命至关重要,感知细胞外营养物质的能力对于协调其摄取和代谢至关重要。共生真菌病原体,例如,已经与人类宿主紧密共同进化,并且很好地适应利用在不同宿主生态位中发现的多种营养物质。不能合成所有氨基酸的人类细胞需要摄取“必需氨基酸”以维持存活。相应地,血液中循环着高水平的氨基酸。宿主蛋白是丰富的氨基酸来源,但其利用取决于蛋白酶将它们切割成较小的肽和游离氨基酸。通过多效性增强它们的摄取并从它们的分解代谢中获取能量以驱动机会性毒力生长来响应细胞外氨基酸。使用……的研究已经建立了理解……中代谢过程的范例;然而,存在根本差异。基于CRISPR/Cas9方法的出现促进了……中的遗传分析,并且正在应用最先进的分子生物学技术直接检查感染宿主体内和原位的生长需求。不同方法的结合可以阐明单个细胞成分的生物学作用。在这里,我们讨论关于营养感知的最新发现,重点是氨基酸摄取和代谢,这些过程是……毒力的基础。