Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment.
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment.
复制标题
巨噬细胞中结核分枝杆菌的转录适应：对吞噬体环境的见解。
DOI：
10.1084/jem.20030846
复制
发表时间：
2003-09-01
影响因子：
15.3
通讯作者：
Schoolnik, GK
中科院分区：
文献类型：
--
作者：
Schnappinger, D;Ehrt, S;Voskuil, MI;Liu, Y;Mangan, JA;Monahan, IM;Dolganov, G;Efron, B;Butcher, PD;Nathan, C;Schoolnik, GK
关键词：
对于含有感染性病原体的吞噬体内的生化环境知之甚少。为了评估这个细胞器的状态，我们捕获了来自野生型和一氧化氮合酶2缺陷小鼠的巨噬细胞中结核分枝杆菌(MTB)在免疫激活前后的转录反应。将吞噬体内转录组与结核分枝杆菌转录组在标准肉汤培养和不同条件下生长期间进行比较，以模拟吞噬环境的特征。作为吞噬体内滞留的结果，差异表达的基因包括干扰素γ和NO诱导的反应，该反应加强了铁清除程序，将微生物从需氧呼吸转换为无氧呼吸，并诱导休眠调节子。对参与脂肪酸活化和β氧化的基因的诱导表明，脂肪酸提供碳和能量。诱导σE依赖、十二烷基硫酸钠调节的基因和参与霉菌酸修饰的基因指向细胞被膜的损伤和修复。吞噬体内转录组中的前哨基因在小鼠的肺中也同样被MTB诱导。因此，微生物转录组作为MTB吞噬体环境的生物探针，表明它是亚硝化的、氧化的、功能性低氧的、碳水化合物贫乏的，并且能够扰乱病原体的细胞膜。
Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2–deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon γ– and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and β-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of σE-dependent, sodium dodecyl sulfate–regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope.
登录
查看更多内容
影响因子：
3.2
作者：
Fisher, MA;Plikaytis, BB;Shinnick, TM
通讯作者：
Shinnick, TM
DOI：
10.1385/0-89603-471-2:285
发表时间：
1998-01-01
期刊：
MYCOBACTERIA PROTOCOLS
影响因子：
--
作者：
Butcher, PD;Mangan, JA;Monahan, IM
通讯作者：
Monahan, IM
影响因子：
56.9
作者：
ARRUDA, S;BOMFIM, G;RILEY, LW
通讯作者：
RILEY, LW
影响因子：
4.4
作者：
Bekker, LG;Freeman, S;Kaplan, G
通讯作者：
Kaplan, G
DOI：
10.1073/pnas.97.3.1252
发表时间：
2000-02-01
影响因子：
11.1
作者：
De Voss, JJ;Rutter, K;Barry, CE
通讯作者：
Barry, CE