Borrelia burgdorferi σ54 is required for mammalian infection and vector transmission but not for tick colonization

Borrelia burgdorferi σ54 is required for mammalian infection and vector transmission but not for tick colonization
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DOI:
10.1073/pnas.0408536102
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发表时间:
2005-04-05
影响因子:
11.1
通讯作者:
Gherardini, FC
Gherardini, FC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fisher, MA;Grimm, D;Gherardini, FC

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先前的研究表明,一个σ(54)-σ(S)级联调控莱姆病病原体伯氏疏螺旋体中少数关键脂蛋白的表达。在此,我们证明这些σ因子,既共同又独立地调控数量多得多的基因和细胞过程。对σ(54)和σ(S)突变株的基因芯片分析确定了305个受σ(54)调控的基因和145个受σ(S)调控的基因,而σ(54)-σ(S)调控级联似乎在伯氏疏螺旋体中控制48个基因。计算机分析显示,在σ(54)突变体中表达改变的基因中近80%与潜在的σ(54)依赖型启动子相关。许多受σ(54)调控的基因在体内表达,并且通过对突变体的基因互补,我们证明伯氏疏螺旋体需要σ(54)来感染哺乳动物。令人惊讶的是,σ(54)突变体能够感染肩突硬蜱,并且在感染后至少能维持24周,这表明σ(54)-σ(S)调控网络不参与蜱中的长期存活。然而,在蜱吸血期间,σ(54)突变体不能进入唾液腺,这表明受σ(54)调控的基因参与传播过程。
Previous studies have shown that a sigma(54)-sigma(S) cascade regulates the expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme disease. Here, we demonstrate that these sigma factors, both together and independently, regulate a much more extensive number of genes and cellular processes. Microarray analyses of sigma(54) and sigma(s) mutant strains identified 305 genes regulated by sigma(54) and 145 regulated by sigma(s), whereas the sigma(54)-sigma(s) regulatory cascade appears to control 48 genes in B. burgdorferi. In silico analyses revealed that nearly 80% of genes with altered expression in the sigma(54) mutant were linked to potential sigma(54)-dependent promoters. Many sigma(54)-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma(54) was required by B. burgdorferi to infect mammals. Surprisingly, sigma(54) mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma(54)-sigma(s) regulatory network was not involved in long-term survival in ticks. However, sigma(54) mutants did not enter the salivary glands during tick feeding, indicating that sigma(54)-regulated genes were involved in the transmission process.