Dissection of the heat-shock response in Myobacterium tuberculosis using mutants and microarrays

Dissection of the heat-shock response in Myobacterium tuberculosis using mutants and microarrays
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DOI:
10.1099/00221287-148-10-3129
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发表时间:
2002-10-01
期刊:
影响因子:
2.8
通讯作者:
Butcher, PD
Butcher, PD
中科院分区:
生物学4区
文献类型:
--
作者:
Stewart, GR;Wernisch, L;Butcher, PD

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热休克蛋白的表达调控在结核分枝杆菌的发病机制中起着重要作用。细菌的热休克反应涉及基因表达的全基因组变化。靶向诱变和全基因组表达谱的组合被用来表征负责控制M.结核确定了两个热休克调节子。HspR作为Hsp 70(DnaK)调节子成员的转录阻遏物,HrcA类似地调节Hsp 60(GroE)应答。这两个特定的阻遏物电路重叠与更广泛的转录变化介导的替代西格玛因子在暴露于高温。一些以前未描述的热休克基因被确定。HspR作为Hsp 70(DnaK)调节子成员的转录阻遏物,HrcA类似地调节Hsp 60(GroE)应答。这两个特定的阻遏物电路重叠与更广泛的转录变化介导的替代西格玛因子在暴露于高温。一些以前未描述的热休克基因被确定为HspR和HrcA调节子的成员。一种新型HspR控制的操纵子编码低分子量α-晶状体蛋白家族的一个成员。这种蛋白质是M.结核热休克反应,并与厌氧应激反应诱导的主要抗原有关。
Regulation of the expression of heat-shock proteins plays an important role in the pathogenesis of Mycobacterium tuberculosis. The heat-shock response of bacteria involves genome-wide changes in gene expression. A combination of targeted mutagenesis and whole-genome expression profiling was used to characterize transcription factors responsible for control of genes encoding the major heat-shock proteins of M. tuberculosis. Two heat-shock regulons were identified. HspR acts as a transcriptional repressor for the members of the Hsp70 (DnaK) regulon, and HrcA similarly regulates the Hsp60 (GroE) response. These two specific repressor circuits overlap with broader transcriptional changes mediated by alternative sigma factors during exposure to high temperatures. Several previously undescribed heat-shock genes were identified. HspR acts as a transcriptional repressor for the members of the Hsp70 (DnaK) regulon, and HrcA similarly regulates the Hsp60 (GroE) response. These two specific repressor circuits overlap with broader transcriptional changes mediated by alternative sigma factors during exposure to high temperatures. Several previously undescribed heat-shock genes were identified as members of the HspR and HrcA regulons. A novel HspR-controlled operon encodes a member of the low-molecular-mass alpha-crystallin family. This protein is one of the most prominent features of the M. tuberculosis heatshock response and is related to a major antigen induced in response to anaerobic stress.