Salmonella enterica serovar Typhimurium uses virulence factors encoded by Salmonella pathogenicity island 1 (SPI-1) to invade the intestinal epithelium. The low oxygen-induced transcriptional regulator LoiA is established to be a positive regulator of SPI-1 genes and can also repress the expression of the ATP-dependent Lon protease, a negative regulator of SPI-1 genes. Whether the repression of lon by LoiA is associated with its regulation of SPI-1 genes, as well as the regulatory mechanism involved, is unknown. In this study, we showed that LoiA directly represses the expression of the lon gene during invasion by binding to the promoter region of lon. The activation of S. Typhimurium SPI-1 gene expression by LoiA is associated with its repression of lon. Moreover, through invasion and mouse infection assays, we found that the repression of lon by LoiA contributes to S. Typhimurium invasion of intestinal epithelial cells and virulence in mice. However, LoiA does not influence lon expression during S. Typhimurium growth in macrophages, which may be associated with the low expression level of loiA in macrophages. Collectively, these findings establish the direct regulation of lon by LoiA and describe a novel mechanism by which LoiA regulates SPI-1 gene expression.

中文翻译：

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LoiA直接抑制lon基因表达以激活沙门氏菌致病岛1基因的表达。

肠炎沙门氏菌鼠伤寒沙门氏菌利用沙门氏菌致病岛1（SPI-1）编码的毒力因子侵袭肠上皮。低氧诱导的转录调节因子LoiA被确立为SPI-1基因的正调节剂，并且还可以抑制ATP依赖性Lon蛋白酶（SPI-1基因的负调节剂）的表达。LoiA抑制lon是否与其对SPI-1基因的调节有关，以及所涉及的调节机制尚不清楚。在这项研究中，我们表明LoiA通过与lon的启动子区域结合而直接抑制lon基因的表达。LoiA对鼠伤寒沙门氏菌SPI-1基因表达的激活与其对lon的抑制有关。此外，通过入侵和小鼠感染检测，我们发现LoiA抑制lon有助于鼠伤寒沙门氏菌侵袭小鼠肠上皮细胞和致病性。但是，LoiA不会影响巨噬细胞中鼠伤寒沙门氏菌生长期间的lon表达，这可能与loiA在巨噬细胞中的低表达水平有关。总的来说，这些发现建立了LoiA对lon的直接调控，并描述了LoiA调控SPI-1基因表达的新机制。