Commonalities of Mycobacterium tuberculosis Transcriptomes in Response to Defined Persisting Macrophage Stresses.
Commonalities of Mycobacterium tuberculosis Transcriptomes in Response to Defined Persisting Macrophage Stresses.
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DOI：
10.3389/fimmu.2022.909904
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
由于细菌的目标是成为细菌，进化对基因表达施加了持续的选择。细胞内病原体结核分枝杆菌，结核病的病原体，已经采取了微调的反应，以生存其宿主的方法，积极根除入侵者。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，RNA-seq进行详细的M.结核菌在与M.结核病在宿主感染，并描绘了一般的应激反应，在持续巨噬细胞应力。M.结核菌长期生长，营养缺乏，缺氧和酸性环境。这些应力之间的共同点指向M。结核病操纵以利用丙酸盐代谢用于脂质合成或在细胞内环境中耐受丙酸盐毒性。虽然几乎所有的压力都导致大多数生物过程的全面关闭，但仅在缺氧M中观察到参与氨基酸，辅因子和脂质合成的途径的上调。结核这些数据揭示了在所有这些持续应激期间特异性或专门诱导的基因和基因群。这些知识可用于设计新的药物靶点或确定可能的M。结核病疫苗开发的脆弱性。此外，从这个基因组的特定功能的破坏将提高我们的进化力量，使结核杆菌是一个非常成功的病原体的理解。
As the goal of a bacterium is to become bacteria, evolution has imposed continued selections for gene expression. The intracellular pathogen Mycobacterium tuberculosis, 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 M. tuberculosis grown in various conditions related to stresses endured by M. tuberculosis during host infection and to delineate a general stress response incurring during persisting macrophage stresses. M. tuberculosis was subjected to long-term growth, nutrient starvation, hypoxic and acidic environments. The commonalities between these stresses point to M. tuberculosis 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 M. tuberculosis. 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 M. tuberculosis 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.
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影响因子：
9.9
作者：
Borah K;Mendum TA;Hawkins ND;Ward JL;Beale MH;Larrouy-Maumus G;Bhatt A;Moulin M;Haertlein M;Strohmeier G;Pichler H;Forsyth VT;Noack S;Goulding CW;McFadden J;Beste DJV
通讯作者：
Beste DJV
影响因子：
3.2
作者：
Fisher, MA;Plikaytis, BB;Shinnick, TM
通讯作者：
Shinnick, TM
影响因子：
3.1
作者：
Bretl, Daniel J.;He, Hongjun;Zahrt, Thomas C.
通讯作者：
Zahrt, Thomas C.
影响因子：
3.1
作者：
Fontan, Patricia;Aris, Virginie;Smith, Issar
通讯作者：
Smith, Issar
APRABC：结核分枝杆菌的复杂特异性基因座，可调节pH驱动的巨噬细胞吞噬体。
影响因子：
3.6
作者：
Abramovitch RB;Rohde KH;Hsu FF;Russell DG
通讯作者：
Russell DG