Senaratne Ryan H, Sidders Ben, Sequeira Patricia, Saunders Grainne, Dunphy Kathleen, Marjanovic Olivera, Reader J Rachel, Lima Patricia, Chan Stephen, Kendall Sharon, McFadden Johnjoe, Riley Lee W
School of Public Health, University of California, Berkeley, CA 94720, USA.
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
J Med Microbiol. 2008 Feb;57(Pt 2):164-170. doi: 10.1099/jmm.0.47454-0.
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 (Deltamce3) and mce4 (Deltamce4) operons and a double deletion mutant (Deltamce3/4). 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 Deltamce3 and the parent strain. However, the bacterial burdens of mice infected with Deltamce4 and Deltamce 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, Deltamce3, Deltamce4 and Deltamce3/4 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 Deltamce4 and Deltamce 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.
结核分枝杆菌基因组包含一个名为mce（mce1 - 4）的操纵子的四个拷贝。此前我们报道，mce1操纵子被破坏的结核分枝杆菌在小鼠中比野生型结核分枝杆菌更具毒力。我们构建了mce3（Δmce3）和mce4（Δmce4）操纵子的单缺失突变体以及一个双缺失突变体（Δmce3/4）。在培养物和巨噬细胞中，所有突变体与野生型（亲本）结核分枝杆菌H37Rv菌株的倍增时间和生长特性相似。此外，在感染Δmce3的小鼠器官中检测到的细菌载量与亲本菌株相似。然而，感染Δmce4和Δmce 3/4的小鼠的细菌载量低于感染亲本菌株的小鼠。感染野生型结核分枝杆菌、Δmce3、Δmce4和Δmce3/4的小鼠的中位生存时间分别为40.5、46、58和62周。感染后15周对肺部进行的组织病理学检查表明，感染Δmce4和Δmce 3/4突变体的小鼠肺部病变程度比感染其他两种菌株的小鼠轻。这些观察结果表明，mce3和mce4操纵子在结核分枝杆菌体内生存中的作用与mce1不同。
