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Pathogenesis in tuberculosis: Transcriptomic approaches to unraveling virulence mechanisms and finding new drug targets

机译:结核病的发病机制:揭示毒力机制和寻找新药物靶标的转录组学方法

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摘要

Tuberculosis (TB) remains a major health problem worldwide. Attempts to control this disease have proved difficult owing to our poor understanding of the pathobiology of Mycobacterium tuberculosis and the emergence of strains that are resistant to multiple drugs currently available for treatment. Genome-wide expression profiling has provided new insight into the transcriptome signatures of the bacterium during infection, notably of macrophages and dendritic cells. These data indicate that M.?tuberculosis expresses numerous genes to evade the host immune responses, to suit its intracellular life style, and to respond to various antibiotic drugs. Among the intracellularly induced genes, several have functions in lipid metabolism, cell wall synthesis, iron uptake, oxidative stress resistance, protein secretion, or inhibition of apoptosis. Herein we review these findings and discuss possible ways to exploit the data to understand the complex etiology of TB and to find new effective drug targets.
机译:结核病(TB)仍然是全球范围内的主要健康问题。由于我们对结核分枝杆菌的病理生物学认识不佳以及出现了对目前可用于治疗的多种药物产生抗药性的菌株,试图控制这种疾病的努力已被证明是困难的。全基因组表达谱分析为细菌在感染过程中,尤其是巨噬细胞和树突状细胞的转录组特征提供了新的见识。这些数据表明,结核分枝杆菌表达许多基因来逃避宿主的免疫反应,以适应其细胞内的生活方式,并对各种抗生素药物产生反应。在细胞内诱导的基因中,有几个在脂质代谢,细胞壁合成,铁摄取,抗氧化应激,蛋白质分泌或细胞凋亡抑制中具有功能。本文中,我们回顾了这些发现,并讨论了利用数据了解结核病的复杂病因并找到新的有效药物靶标的可能方法。

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