Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice
Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice
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DOI：
10.1099/jmm.0.47454-0
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发表时间：
2008-02-01
影响因子：
3
通讯作者：
Riley, Lee W.
中科院分区：
文献类型：
--
作者：
Senaratne, Ryan H.;Sidders, Ben;Riley, Lee W.
结核分枝杆菌基因组包含四个拷贝的称为mce（mce 1 -4）的操纵子。此前，我们报道了M。在mce 1操纵子中被破坏的结核杆菌比野生型结核杆菌毒力更强。小鼠肺结核我们在mce 3（Δ mce 3）和mce 4（Δ mce 4）操纵子和一个双缺失突变体（Δ mce 3/4）中产生了单缺失突变体。所有突变体和野生型（亲本）M观察到相似的倍增时间和生长特性。结核病H37 Rv菌株在培养物和巨噬细胞中的表达。此外，在感染Delta mce 3和亲本菌株的小鼠器官中检测到相似的细菌负荷。然而，感染Delta mce 4和Delta mce 3/4的小鼠的细菌负荷低于感染亲本菌株的小鼠。野生型M.肺结核、Delta mce 3、Delta mce 4和Delta mce 3/4分别为40.5、46、58和62周。感染后15周的肺部组织学检查显示，感染Delta mce 4和Delta mce 3/4突变体的小鼠的肺部病变程度不如感染其他两种菌株的小鼠显著。这些观察结果表明，mce 3和mce 4操纵子有一个不同于mce 1的作用，在体内生存的M。结核
The Mycobacterium tuberculosis genome contains four copies of an operon called mce (mce1-4). Previously we reported that M. tuberculosis disrupted in the mce1 operon is more virulent than wild-type M. tuberculosis in mice. We generated single deletion mutants in mce3 (Delta mce3) and mce4 (Delta mce4) operons and a double deletion mutant (Delta mce3/4). Similar doubling times and growth characteristics were observed for all mutants and the wild-type (parent) M. tuberculosis H37Rv strain in culture and in macrophages. In addition, similar bacterial burdens were detected in organs from mice infected with Delta mce3 and the parent strain. However, the bacterial burdens of mice infected with Delta mce4 and Delta mce 3/4 were less than those of mice infected with the parent strain. The median survival times of mice infected with wild-type M. tuberculosis, Delta mce3, Delta mce4 and Delta mce3/4 were 40.5, 46, 58 and 62 weeks, respectively. Histopathological examination of lungs at 15 weeks post-infection showed that the extent of the lung lesions was less prominent in mice infected with Delta mce4 and Delta mce 3/4 mutants than in mice infected with the other two strains. These observations suggest that the mce3 and mce4 operons have a role distinct from that of mce1 for in vivo survival of M. tuberculosis.