Mce2 operon mutant strain of Mycobacterium tuberculosis is attenuated in C57BL/6 mice.
Mce2 operon mutant strain of Mycobacterium tuberculosis is attenuated in C57BL/6 mice.
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DOI：
10.1016/j.tube.2009.10.004
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Riley LW
中科院分区：
文献类型：
--
作者：
Marjanovic O;Miyata T;Goodridge A;Kendall LV;Riley LW
结核分枝杆菌基因组包含四组相关的操纵子，称为 mce (mce1-4)。这些操纵子之一 mce1 的破坏会导致结核分枝杆菌变得高毒力，而 mce3 和 mce4 操纵子突变体在小鼠中则减弱。本研究检查了 mce2 操纵子突变体的表型。结核分枝杆菌 H37Rv 中 mce2 操纵子的缺失对 7H9 液体肉汤中的细菌生长或巨噬细胞内的存活没有影响。然而，感染突变株的 RAW 巨噬细胞样细胞产生 TNF-α、IL-6 和 MCP-1 的能力降低。在 C57BL/6 小鼠肺中，mce2 操纵子突变体和野生型 H37Rv 在感染长达 20 周内以类似方式进行复制。然而，到感染56周时，所有感染野生型H37Rv的小鼠均死亡，而感染突变型的小鼠中80%仍存活（P<0.0001）。在感染相同时间段内，感染突变体的小鼠中受影响的肺实质的比例显着低于感染野生型的小鼠。这些观察结果表明，mce2操纵子突变体是减毒的，这种减毒与细菌负荷无关，而是与突变体引发不利于动物生存的免疫反应和肺部病理的能力下降有关。
Mycobacterium tuberculosis genome contains four related sets of an operon called mce (mce1-4). The disruption of one of these operons, mce1, causes M. tuberculosis to become hypervirulent, whereas the mce3 and mce4 operon mutants are attenuated in mice. This study examined the phenotype of the mce2 operon mutant. The deletion of mce2 operon in M. tuberculosis H37Rv had no effect on bacterial growth in 7H9 liquid broth or survival within macrophages. However, RAW macrophage-like cells infected with the mutant strain were reduced in their ability to produce TNF-α, IL-6 and MCP-1. In C57BL/6 mouse lungs, the mce2 operon mutant and wild type H37Rv replicated similarly up to 20 weeks of infection. However, by 56 weeks of infection, all mice infected with the wild type H37Rv had died, while 80% of those infected with the mutant remained alive (P< 0.0001). The proportion of affected lung parenchyma in mice infected with the mutant was substantially less than that of mice infected with the wild type for the same time periods of infection. These observations suggest that the mce2 operon mutant is attenuated, and that this attenuation is related not to the bacterial burden but to the mutant’s decreased ability to elicit a type of immune response and lung pathology detrimental to the survival of the animal.
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影响因子：
3.4
作者：
Uchida, Yujiro;Casali, Nicola;Riley, Lee W.
通讯作者：
Riley, Lee W.
影响因子：
56.9
作者：
ARRUDA, S;BOMFIM, G;RILEY, LW
通讯作者：
RILEY, LW
影响因子：
3.2
作者：
de la Paz Santangelo, Maria;Blanco, Federico;Bigi, Fabiana
通讯作者：
Bigi, Fabiana
DOI：
10.1073/pnas.0306023101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Talaat, AM;Lyons, R;Johnston, SA
通讯作者：
Johnston, SA
影响因子：
2.8
作者：
Parish, T;Stoker, NG
通讯作者：
Stoker, NG