The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice
The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice
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DOI：
10.1073/pnas.1631248100
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发表时间：
2003-08-19
影响因子：
11.1
通讯作者：
Barry, CE
中科院分区：
文献类型：
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作者：
Dahl, JL;Kraus, CN;Barry, CE
非复制型结核分枝杆菌（Mtb）的长期生存是通过一个广泛的转录程序（称为严格反应）协调关闭活性代谢来确保的。在Mtb中，这种反应是由Rel（Mtb）的酶促作用引发的，并且Rel（Mtb）的缺失产生在维持长期活力方面严重受损的菌株（H37RvDeltarel（mtb））。尽管用H37RvDeltarel（Mtb）气溶胶接种小鼠导致正常的初始细菌生长和遏制，但该菌株维持慢性感染的能力严重受损。在整个感染过程中，与对照组相比，用H37RvDeltarel（Mtb）感染的小鼠的肺和脾中注意到显著的组织病理学差异。微阵列分析显示，H371RvDeltarel（Mtb）遭受的转录装置的普遍改变，以及毒力因子，细胞壁生物合成酶，热休克蛋白，和分泌的抗原，可能会改变重组生物体的免疫识别的表达的具体变化。因此，Rel（Mtb）通过改变可能有助于成功潜伏感染的抗原和酶因子的表达，对于在小鼠中成功建立持续感染至关重要。
Long-term survival of nonreplicating Mycobacterium tuberculosis (Mtb) is ensured by the coordinated shutdown of active metabolism through a broad transcriptional program called the stringent response. In Mtb, this response is initiated by the enzymatic action of Rel(Mtb) and deletion of rel(Mtb) produces a strain (H37RvDeltarel(mtb)) severely compromised in the maintenance of long-term viability. Although aerosol inoculation of mice with H37RvDeltarel(Mtb) results in normal initial bacterial growth and containment, the ability of this strain to sustain chronic infection is severely impaired. Significant histopathologic differences were noted in lungs and spleens of mice infected with H37RvDeltarel(Mtb) compared with controls throughout the course of the infection. Microarray analysis revealed that H371RvDeltarel(Mtb) suffers from a generalized alteration of the transcriptional apparatus, as well as specific changes in the expression of virulence factors, cell-wall biosynthetic enzymes, heat shock proteins, and secreted antigens that may alter immune recognition of the recombinant organism. Thus, Rel(Mtb) is critical for the successful establishment of persistent infection in mice by altering the expression of antigenic and enzymatic factors that may contribute to successful latent infection.