The RNA polymerase‐binding protein DksA, together with the alarmone nucleotides (p)ppGpp, mediates the stringent response to nutrient starvation in Borrelia burgdorferi . To date, the contribution of DksA to B. burgdorferi infection remains unknown. We report here that DksA is essential for B. burgdorferi to infect a mammalian host. dksA expression was highly induced during infection. Moreover, a dksA‐deficient mutant was incapable of infecting mice. The mutant displayed growth defects when cultured in vitro and resistance to osmotic pressure was markedly reduced. These phenotypes were fully restored to those of the wild type when dksA mutation was complemented. We further showed that DksA controlled the expression of virulence‐associated lipoprotein OspC, likely via the central alternative sigma factor RpoS. Synthesis of RpoS was abolished in the dksA mutant, but rpoS transcription remained unaffected. Additionally, we found that the expression of clpX , clpA , clpP , and clpP2 was significantly increased in the mutant, suggesting that DksA may post‐transcriptionally regulate rpoS expression via its effect on ClpXP and/or ClpAP proteases. These combined data demonstrate that DksA regulates B. burgdorferi virulence at least partially through its influence on RpoS and OspC. This study thus elucidates that, in addition to function as a stringent response regulator, DksA promotes the transcription and/or translation of genes contributing to B. burgdorferi infectivity.

中文翻译：

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DksA 在调节伯氏疏螺旋体的毒力方面起着至关重要的作用。

RNA 聚合酶结合蛋白 DksA 与警报核苷酸 (p)ppGpp 一起介导了伯氏疏螺旋体对营养饥饿的严格反应。迄今为止，DksA 对伯氏疏螺旋体感染的贡献仍然未知。我们在此报告 DksA 对伯氏疏螺旋体感染哺乳动物宿主至关重要。dksA表达在感染过程中被高度诱导。此外，dksA 缺陷型突变体无法感染小鼠。该突变体在体外培养时表现出生长缺陷，对渗透压的抵抗力显着降低。当dksA时，这些表型完全恢复到野生型突变得到补充。我们进一步表明，DksA 可能通过中央替代 sigma 因子 RpoS 控制毒力相关脂蛋白 OspC 的表达。RpoS 的合成在dksA突变体中被取消，但rpoS转录不受影响。此外，我们发现突变体中clpX、clpA、clpP和clpP2的表达显着增加，表明 DksA 可能通过其对 ClpXP 和/或 ClpAP 蛋白酶的影响在转录后调节rpoS表达。这些组合数据表明 DksA 调节B. burgdorferi毒力至少部分是通过其对 RpoS 和 OspC 的影响。因此，这项研究阐明，除了作为严格的反应调节器之外，DksA 还促进了对伯氏疏螺旋体感染性有贡献的基因的转录和/或翻译。