Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Virulence. 2021 Dec;12(1):2750-2763. doi: 10.1080/21505594.2021.1995253.
DksA with (p)ppGpp regulates a wide range of gene transcriptions during the stringent response. The aim of this study was to identify a DksA ortholog in and clarify the roles of DksA in bacterial physiology and virulence. The ∆ mutant and its complemented strains were constructed using ATCC 17978. The in ATCC 17978 was identified to using sequence homology, protein structure prediction, and gene expression patterns under different culture conditions. The ∆ mutant strain showed a filamentous morphology compared with the wild-type (WT) strain. Bacterial growth was decreased in the ∆ mutant strain under static conditions. Surface motility was decreased in the ∆ mutant strain compared with the WT strain. In contrast, biofilm formation was increased and biofilm-associated genes, such as and , were upregulated in the ∆ mutant strain. The ∆ mutant strain produced less autoinducers than the WT strain. The expression of and was significantly decreased in the ∆ mutant strain. Furthermore, the ∆ mutant strain showed less bacterial burden and milder histopathological changes in the lungs of mice than the WT strain. Mice survival was also significantly different between the ∆ mutant and WT strains. Conclusively, DksA is directly or indirectly involved in regulating a wide range of genes associated with bacterial physiology and virulence, which contributes to the pathogenesis of . Thus, DksA is a potential anti-virulence target for infection.
DksA 与 (p)ppGpp 在严谨反应期间调节广泛的基因转录。本研究的目的是鉴定 中的 DksA 同源物，并阐明 DksA 在细菌生理学和毒力中的作用。使用 ATCC 17978 构建了 ∆突变体及其互补菌株。使用序列同源性、蛋白质结构预测和不同培养条件下的基因表达模式，鉴定出 ATCC 17978 中的 。与野生型 (WT) 菌株相比，∆突变体菌株表现出丝状形态。在静态条件下，∆突变体菌株的细菌生长减少。与 WT 菌株相比，∆突变体菌株的表面运动性降低。相比之下，∆突变体菌株的生物膜形成增加，生物膜相关基因，如 和 ，上调。∆突变体菌株产生的自体诱导物比 WT 菌株少。∆突变体菌株中 和 的表达显著降低。此外，与 WT 菌株相比，∆突变体菌株在小鼠肺部的细菌负荷较低，组织病理学变化较轻。小鼠存活率也在 ∆突变体和 WT 菌株之间存在显著差异。总之，DksA 直接或间接地参与调节与细菌生理学和毒力相关的广泛基因，这有助于 的发病机制。因此，DksA 是 感染的潜在抗毒力靶标。
