Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients
Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients
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DOI：
10.1073/pnas.2436197100
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发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
McKinney, JD
中科院分区：
文献类型：
--
作者：
Timm, J;Post, FA;McKinney, JD
促进结核分枝杆菌 (MTB) 在哺乳动物宿主中进入、复制和持久存在的致病过程可能包括特定基因组在感染不同阶段的调节表达。体内差异表达基因的鉴定将有助于深入了解结核病（TB）中宿主与病原体的相互作用；这种方法对于人类结核病的研究可能特别有价值，因为人类结核病的实验机会有限。在本研究中，对无菌培养物中的体外、小鼠肺的体内以及从患有活动性疾病的结核病患者获得的肺标本中对所选MTB mRNA的水平进行了定量。我们报告了野生型 C57BL/6 小鼠肺部与体外培养的细菌相比，与铁限制、替代碳代谢和细胞缺氧相关的 MTB mRNA 的差异表达，这些条件被认为存在于野生型 C57BL/6 小鼠肺部的结核肉芽肿病变中。对从结核病患者获得的肺标本中的同一组 mRNA 进行分析，发现人类与小鼠的 MTB 基因表达存在差异。
Pathogenetic processes that facilitate the entry, replication, and persistence of Mycobacterium tuberculosis (MTB) in the mammalian host likely include the regulated expression of specific sets of genes at different stages of infection. Identification of genes that are differentially expressed in vivo would provide insights into host-pathogen interactions in tuberculosis (TB); this approach might be particularly valuable for the study of human TB, where experimental opportunities are limited. In this study, the levels of selected MTB mRNAs were quantified in vitro in axenic culture, in vivo in the lungs of mice, and in lung specimens obtained from TB patients with active disease. We report the differential expression of MTB mRNAs associated with iron limitation, alternative carbon metabolism, and cellular hypoxia, conditions that are thought to exist within the granulomatous lesions of TB, in the lungs of wild-type C57BL/6 mice as compared with bacteria grown in vitro. Analysis of the same set of mRNAs in lung specimens obtained from TB patients revealed differences in MTB gene expression in humans as compared with mice.