Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, 08028 Barcelona, Spain.
Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187 Umeå, Sweden.
Int J Mol Sci. 2022 Oct 14;23(20):12256. doi: 10.3390/ijms232012256.
ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. In , ppGpp regulates the expression of cellular factors that are important during urinary tract infections. Here, we characterize the role of this alarmone in the regulation of the operon of the UPEC isolate J96, encoding the toxin α-hemolysin that induces cytotoxicity during infection of bladder epithelial cells. ppGpp is required for the expression of the α-hemolysin encoded in by stimulating its transcriptional expression. Prototrophy suppressor mutations in a ppGpp-deficient strain restore the α-hemolysin expression from this operon to wild-type levels, confirming the requirement of ppGpp for its expression. ppGpp stimulates expression independently of RpoS, RfaH, Zur, and H-NS. The expression of is promoted at 37 °C and at low osmolarity. ppGpp is required for the thermoregulation but not for the osmoregulation of the operon. Studies in both commensal and UPEC isolates demonstrate that no UPEC specific factor is strictly required for the ppGpp-mediated regulation described. Our data further support the role of ppGpp participating in the coordinated regulation of the expression of bacterial factors required during infection.
ppGpp 是一种细胞内传感器，它可以响应不同类型的应激，协调细菌基因表达模式的重排，促进适应和生存新的环境条件。最初被描述为调节代谢适应性反应，ppGpp 调节属于非常不同功能类别的基因的表达。在 中，ppGpp 调节细胞因子的表达，这些因子在尿路感染中很重要。在这里，我们描述了这种警报素在调节 UPEC 分离株 J96 的 操纵子表达中的作用，该操纵子编码α-溶血素，在感染膀胱上皮细胞时诱导细胞毒性。ppGpp 通过刺激其转录表达，对 编码的α-溶血素的表达是必需的。在缺乏 ppGpp 的菌株中，原养型抑制突变恢复了该操纵子中α-溶血素的表达，使其达到野生型水平，这证实了 ppGpp 对其表达的必要性。ppGpp 独立于 RpoS、RfaH、Zur 和 H-NS 刺激 表达。在 37°C 和低渗透压下，表达 。ppGpp 是 操纵子的热调节所必需的，但不是渗透压调节所必需的。在共生和 UPEC 分离株中的研究表明，ppGpp 介导的调节不需要 UPEC 特定的因子。我们的数据进一步支持了 ppGpp 参与感染过程中所需细菌因子的协调表达调控的作用。
