Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis
Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis
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DOI：
10.1128/iai.71.3.1134-1140.2003
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发表时间：
2003-03-01
影响因子：
3.1
通讯作者：
Stoker, NG
中科院分区：
文献类型：
--
作者：
Parish, T;Smith, DA;Stoker, NG
双组分调节信号转导系统广泛分布于细菌中，使生物体能够响应各种环境刺激而在基因表达中做出协调变化。结核分枝杆菌的基因组序列包含11个完整的双组分系统、4个分离的同源调节子和3个分离的同源感受器。我们已经在这些基因中的六个中构建了定义的突变，并在SCID小鼠模型中测量了毒力。感染四种突变体（devR、tcrXY、trcS和kdpDE缺失）的小鼠比感染野生型细菌的小鼠死亡更快。另外两个突变体（narL和Rv3220c）与野生型H37Rv菌株相比没有显示出变化。最高毒力的突变体（devRDelta）也增长得更快，在免疫活性小鼠和γ干扰素激活的巨噬细胞感染的急性阶段。这些结果定义了一类新的基因在这种病原体的存在减缓其在体内的繁殖或增加其易感性宿主杀伤机制。因此，M。结核病积极地维持自身生存与宿主生存之间的平衡。
Two-component regulatory signal transduction systems are widely distributed among bacteria and enable the organisms to make coordinated changes in gene expression in response to a variety of environmental stimuli. The genome sequence of Mycobacterium tuberculosis contains 11 complete two-component systems, four isolated homologous regulators, and three isolated homologous sensors. We have constructed defined mutations in six of these genes and measured virulence in a SCID mouse model. Mice infected with four of the mutants (deletions of devR, tcrXY, trcS, and kdpDE) died more rapidly than those infected with wild-type bacteria. The other two mutants (narL and Rv3220c) showed no change compared to the wild-type H37Rv strain. The most hypervirulent mutant (devRDelta) also grew more rapidly in the acute stage of infection in immunocompetent mice and in gamma interferon-activated macrophages. These results define a novel class of genes in this pathogen whose presence slows down its multiplication in vivo or increases its susceptibility to host killing mechanisms. Thus, M. tuberculosis actively maintains a balance between its own survival and that of the host.