sodA is essential for virulence of Borrelia burgdorferi in the murine model of Lyme disease
sodA is essential for virulence of Borrelia burgdorferi in the murine model of Lyme disease
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DOI：
10.1111/j.1365-2958.2008.06549.x
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发表时间：
2009-02-01
影响因子：
3.6
通讯作者：
Seshu, J.
中科院分区：
文献类型：
--
作者：
Esteve-Gassent, Maria D.;Elliott, Nathaniel L.;Seshu, J.
伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病的病原体，其拥有一组有限的基因来对抗在蜱虫媒介或哺乳动物宿主体内遇到的氧化/亚硝化应激。我们使编码超氧化物歧化酶A（sodA，bb0153）的基因失活，该酶介导超氧阴离子的歧化反应，并检测了该突变体的体外和体内表型。与对照菌株相比，sodA突变体的体外生长特性没有显著差异。对螺旋体活力的显微镜分析显示，与对照相比，用超氧化物生成剂处理sodA突变体时细胞死亡的百分比更高。在每只C3H/HeN小鼠皮内注射10³或10⁵个螺旋体后进行的感染性分析表明，在感染后21天，与对照菌株相比，sodA突变体的感染性完全减弱。sodA突变体对活化的巨噬细胞和中性粒细胞的作用更敏感，这表明其体内表型部分是由于活化的免疫细胞的杀伤作用。这些研究表明，SodA在对抗氧化应激中起重要作用，并且对伯氏疏螺旋体在莱姆病小鼠模型中的定植和传播至关重要。
Borrelia burgdorferi, the causative agent of Lyme disease, has a limited set of genes to combat oxidative/nitrosative stress encountered in its tick vector or mammalian hosts. We inactivated the gene encoding for superoxide dismutase A (sodA, bb0153), an enzyme mediating the dismutation of superoxide anions and examined the in vitro and in vivo phenotype of the mutant. There were no significant differences in the in vitro growth characteristics of the sodA mutant compared with the control strains. Microscopic analysis of viability of spirochaetes revealed greater percentage of cell death upon treatment of sodA mutant with superoxide generators compared with its controls. Infectivity analysis in C3H/HeN mice following intradermal needle inoculation of 103 or 105 spirochaetes per mouse revealed complete attenuation of infectivity for the sodA mutant compared with control strains at 21 days post infection. The sodA mutant was more susceptible to the effects of activated macrophages and neutrophils, suggesting that its in vivo phenotype is partly due to the killing effects of activated immune cells. These studies indicate that SodA plays an important role in combating oxidative stress and is essential for the colonization and dissemination of B. burgdorferi in the murine model of Lyme disease.