Cheruvu Mani, Plikaytis Bonnie B, Shinnick Thomas M
Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Mail stop G35, 1600 Clifton Rd., Atlanta, GA 30333, USA.
Tuberculosis (Edinb). 2007 Jan;87(1):12-20. doi: 10.1016/j.tube.2006.01.021. Epub 2006 Aug 8.
The Rv3083-Rv3089 operon of Mycobacterium tuberculosis has been shown to be induced 17-33-fold when tubercle bacilli were exposed in vitro to acidic conditions which may mimic those that the bacilli encounter early during the infection and it is induced during growth in macrophages. To understand the role of this operon in intracellular survival, we constructed a knockout of the operon in the M. tuberculosis H37Rv strain. No differences were observed in the growth of mutant and wild-type mycobacteria on axenic media. Though the uptake of mutant and wild-type bacteria by eukaryotic cells was similar, the mutant failed to grow subsequently. By 192h post-infection, the fold differences between the wild-type and mutant bacteria were significant thus leading to the conclusion that the mutant is defective for intracellular growth in these cell lines. Complementation of the knockout restored intracellular growth to wild-type levels. During the first 24-48h post-infection, mutant bacteria also stimulated production of significantly less IL-1beta, IL-6, IL-8, RANTES, and MCP-1 by THP-1 cells than wild-type bacteria. Overall, the data indicate that the operon plays an important role in the ability of M. tuberculosis to grow inside host cells.
结核分枝杆菌的Rv3083 - Rv3089操纵子已被证明，当结核杆菌在体外暴露于可能模拟其在感染早期遇到的酸性条件下时，会被诱导17 - 33倍，并且在巨噬细胞中生长时也会被诱导。为了了解该操纵子在细胞内存活中的作用，我们构建了结核分枝杆菌H37Rv菌株中该操纵子的敲除菌株。在无菌培养基上，突变型和野生型分枝杆菌的生长未观察到差异。虽然真核细胞对突变型和野生型细菌的摄取相似，但突变型随后无法生长。感染后192小时，野生型和突变型细菌之间的倍数差异显著，因此得出结论，该突变型在这些细胞系中的细胞内生长存在缺陷。敲除菌株的互补作用将细胞内生长恢复到野生型水平。在感染后的最初24 - 48小时内，突变型细菌刺激THP - 1细胞产生的IL - 1β、IL - 6、IL - 8、RANTES和MCP - 1也明显少于野生型细菌。总体而言，数据表明该操纵子在结核分枝杆菌在宿主细胞内生长的能力中起重要作用。
