The BosR regulatory protein of Borrelia burgdorferi interfaces with the RpoS regulatory pathway and modulates both the oxidative stress response and pathogenic properties of the Lyme disease spirochete.
The BosR regulatory protein of Borrelia burgdorferi interfaces with the RpoS regulatory pathway and modulates both the oxidative stress response and pathogenic properties of the Lyme disease spirochete.
复制标题
DOI：
10.1111/j.1365-2958.2009.06951.x
复制
发表时间：
2009-12
影响因子：
3.6
通讯作者：
Skare JT
中科院分区：
文献类型：
--
作者：
Hyde JA;Shaw DK;Smith Iii R;Trzeciakowski JP;Skare JT
伯氏疏螺旋体，即莱姆病螺旋体，在其感染的节肢动物和哺乳动物宿主之间转移时会发生适应性变化。我们假设BosR在伯氏疏螺旋体中作为一种全局调控因子，调节氧化应激反应并适应哺乳动物宿主。为了验证这一假设，我们在一个低传代的伯氏疏螺旋体分离株中构建了一个bosR突变体。所得到的bosR::kanR菌株在微需氧或厌氧条件下生长时发生了改变，这表明BosR在这两种生长条件下都是最佳复制所必需的。BosR的缺失增加了伯氏疏螺旋体对过氧化氢的敏感性，并减少了Cdr和NapA的合成，这两种蛋白分别对细胞氧化还原平衡和氧化应激反应很重要，这表明BosR在疏螺旋体的氧化稳态中具有重要作用。对于bosR突变体，RpoS的产生被阻断，导致OspC和DbpA的缺失，这表明BosR与RpoS - RpoN - Rrp2调控级联相互作用。与和RpoS的联系一致，缺乏bosR的细胞在感染小鼠模型中无感染性。这些结果表明，BosR是抵抗氧化应激源所必需的，并提供了一种对伯氏疏螺旋体致病机制必要的调控反应。
Borrelia burgdorferi, the Lyme disease spirochete, adapts as it moves between the arthropod and mammalian hosts that it infects. We hypothesize that BosR serves as a global regulator in B. burgdorferi to modulate the oxidative stress response and adapt to mammalian hosts. To test this hypothesis, a bosR mutant in a low passage B. burgdorferi isolate was constructed. The resulting bosR::kanR strain was altered when grown microaerobically or anaerobically suggesting that BosR is required for optimal replication under both growth conditions. The absence of BosR increased the sensitivity of B. burgdorferi to hydrogen peroxide and reduced the synthesis of Cdr and NapA, proteins important for cellular redox balance and the oxidative stress response, respectively, suggesting an important role for BosR in borrelial oxidative homeostasis. For the bosR mutant, the production of RpoS was abrogated and resulted in the loss of OspC and DbpA, suggesting that BosR interfaces with the RpoS-RpoN-Rrp2 regulatory cascade. Consistent with the linkage to RpoS, cells lacking bosR were non-infectious in the mouse model of infection. These results indicate that BosR is required for resistance to oxidative stressors and provides a regulatory response that is necessary for B. burgdorferi pathogenesis.
登录
查看更多内容
影响因子：
3.2
作者：
Fuangthong, M;Herbig, AF;Helmann, JD
通讯作者：
Helmann, JD
DOI：
10.1073/pnas.0408536102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Fisher, MA;Grimm, D;Gherardini, FC
通讯作者：
Gherardini, FC
DOI：
10.1073/pnas.231442498
发表时间：
2001-10-23
影响因子：
11.1
作者：
Hübner, A;Yang, XF;Norgard, MV
通讯作者：
Norgard, MV
影响因子：
3.6
作者：
Bsat, N;Herbig, A;Helmann, JD
通讯作者：
Helmann, JD
影响因子：
3.6
作者：
Esteve-Gassent, Maria D.;Elliott, Nathaniel L.;Seshu, J.
通讯作者：
Seshu, J.