Lewis Kaeryn N, Liao Reiling, Guinn Kristi M, Hickey Mark J, Smith Sherilyn, Behr Marcel A, Sherman David R
Department of Pediatrics, University of Washington, Seattle 98195, USA.
J Infect Dis. 2003 Jan 1;187(1):117-23. doi: 10.1086/345862. Epub 2002 Dec 2.
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5-kb region are of unknown function, although they include the TB-specific immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections of the human macrophage-like cell line THP-1, human peripheral blood monocyte-derived macrophages, and C57BL/6 mice. In each of these systems, the H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar to BCG controls. Therefore, it was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation.
结核（TB）疫苗卡介苗（BCG）是一种减毒活生物体，但其减毒所涉及的突变从未明确。最近的遗传学研究确定了一个单一的差异DNA区域，即RD1，它在所有卡介苗菌株中均不存在，而在所有结核分枝杆菌（MTB）菌株中都存在。尽管该9.5 kb区域内预测的9个开放阅读框包含结核特异性免疫显性抗原ESAT-6和CFP-10，但其功能未知。在本研究中，从MTB菌株H37Rv中删除了RD1，并在感染人巨噬细胞样细胞系THP-1、人外周血单核细胞衍生巨噬细胞和C57BL/6小鼠后评估了H37Rv:DeltaRD1的毒力。在上述每个系统中，H37Rv:DeltaRD1菌株的毒力均显著低于MTB，且与卡介苗对照非常相似。因此，得出的结论是，RD1内或受其控制的基因对MTB毒力至关重要，且RD1的缺失在卡介苗减毒过程中起重要作用。
