Abstract：
Salmonella Typhimurium is a Gram-negative intestinal pathogen that can infect humans and a variety of animals, causing gastroenteritis or serious systemic infection. Replication within host macrophages is essential for S. Typhimurium to cause systemic infection. By analyzing transcriptome data, the expression of yhjC gene, which encodes a putative regulator in S. Typhimurium, was found to be significantly up-regulated after the internalization of Salmonella by macrophages. Whether yhjC gene is involved in S. Typhimurium systemic infection and the related mechanisms were investigated in this study. The deletion of yhjC reduced the replication ability of S. Typhimurium in macrophages and decreased the colonization of S. Typhimurium in mouse systemic organs (liver and spleen), while increasing the survival rate of the infected mice, suggesting that YhjC protein promotes systemic infection by S. Typhimurium. Furthermore, by using transcriptome sequencing and RT-qPCR assay, the transcription of several virulence genes, including spvD, iroCDE and zraP, was found to be down-regulated after the deletion of yhjC. Electrophoretic mobility shift assay showed that YhjC protein can directly bind to the promoter region of spvD and zraP to promote their transcription. These findings suggest that YhjC contributes to the systemic virulence of S. Typhimurium via the regulation of multiple virulence genes and YhjC could represent a promising target to control S. Typhimurium infection.
摘要：
鼠伤寒沙门氏菌是一种革兰氏阴性肠道病原体，可以感染人类和多种动物，引起胃肠炎或严重的全身感染。宿主巨噬细胞内的复制是鼠伤寒沙门氏菌引起全身感染所必需的。通过分析转录组数据，YHJC基因的表达，在鼠伤寒沙门氏菌中编码一个推定的调节因子，被发现在巨噬细胞内化沙门氏菌后显著上调。本研究探讨了yhjC基因是否参与鼠伤寒沙门氏菌全身感染及其相关机制。yhjC的缺失降低了鼠伤寒沙门氏菌在巨噬细胞中的复制能力，并降低了鼠伤寒沙门氏菌在小鼠全身器官（肝脏和脾脏）中的定植，同时提高被感染小鼠的存活率，提示YhjC蛋白促进鼠伤寒沙门氏菌的全身感染。此外，通过使用转录组测序和RT-qPCR分析，几个毒力基因的转录，包括spvD,iroCDE和zraP,发现在yhjC缺失后下调。电泳迁移率变化分析表明，YhjC蛋白可直接与spvD和zraP的启动子区结合，促进其转录。这些发现表明YhjC通过调节多个毒力基因而有助于鼠伤寒沙门氏菌的全身毒力，YhjC可能是控制鼠伤寒沙门氏菌感染的有希望的靶标。
