Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States.
Research Department, Genome Biology Division, New England Biolabs Inc., Ipswich, MA, United States.
Front Immunol. 2022 Jul 1;13:909904. doi: 10.3389/fimmu.2022.909904. eCollection 2022.
As the goal of a bacterium is to become bacteria, evolution has imposed continued selections for gene expression. The intracellular pathogen , the causative agent of tuberculosis, has adopted a fine-tuned response to survive its host's methods to aggressively eradicate invaders. The development of microarrays and later RNA sequencing has led to a better understanding of biological processes controlling the relationship between host and pathogens. In this study, RNA-seq was performed to detail the transcriptomes of grown in various conditions related to stresses endured by during host infection and to delineate a general stress response incurring during persisting macrophage stresses. was subjected to long-term growth, nutrient starvation, hypoxic and acidic environments. The commonalities between these stresses point to maneuvering to exploit propionate metabolism for lipid synthesis or to withstand propionate toxicity whilst in the intracellular environment. While nearly all stresses led to a general shutdown of most biological processes, up-regulation of pathways involved in the synthesis of amino acids, cofactors, and lipids were observed only in hypoxic . This data reveals genes and gene cohorts that are specifically or exclusively induced during all of these persisting stresses. Such knowledge could be used to design novel drug targets or to define possible vulnerabilities for vaccine development. Furthermore, the disruption of specific functions from this gene set will enhance our understanding of the evolutionary forces that have caused the tubercle bacillus to be a highly successful pathogen.
作为细菌的目标是成为细菌，进化已经施加了持续的选择，以促进基因表达。细胞内病原体，即结核病的病原体，已经采取了精细的反应来生存，以应对宿主积极根除入侵者的方法。微阵列和后来的 RNA 测序的发展，使我们更好地理解了控制宿主和病原体之间关系的生物过程。在这项研究中，进行了 RNA-seq，以详细描述在与宿主感染期间承受的压力相关的各种条件下生长的转录组，并描绘在持续巨噬细胞压力下发生的一般应激反应。被暴露于长期生长、营养饥饿、缺氧和酸性环境中。这些压力之间的共同点表明，在细胞内环境中，细菌会操纵利用丙酸代谢来合成脂质，或耐受丙酸毒性。虽然几乎所有的压力都会导致大多数生物过程的普遍关闭，但只有在缺氧时才会观察到参与氨基酸、辅助因子和脂质合成的途径的上调。这些数据揭示了在所有这些持续的压力下特异性或专门诱导的基因和基因簇。这种知识可以用于设计新的药物靶点，或定义可能用于疫苗开发的可能的弱点。此外，破坏该基因集的特定功能将增强我们对导致结核分枝杆菌成为高度成功病原体的进化力量的理解。
