志贺氏菌是主要感染人结肠并引起志贺氏菌病的细胞内病原体。志贺氏菌的毒力很大程度上依赖于III型分泌系统(T3SS)和分泌效应物。VirF,主要的志贺氏菌毒力调节剂,对T3SS相关基因的表达至关重要。在这项研究中,我们发现YhjC,LysR型转录调节因子,通过激活virF的转录对志贺氏菌毒力是必需的。yhjC突变体的致病性,包括在豚鼠结肠中的定植以及其对宿主细胞粘附和侵袭的能力,显着降低。virF和几乎所有的VirF依赖性基因的表达水平被yhjC缺失下调,表明YhjC可以激活virF转录。电泳迁移率变化分析证明YhjC可以直接结合virF启动子区。因此,YhjC是一种新型的毒力调节剂,可积极调节virF的表达并促进志贺氏菌的毒力。此外,全基因组表达分析确定了在大毒力质粒中存在其他基因,并且基因组对yhjC缺失表现出差异表达,有169个下调基因和99个上调基因,这表明YhjC也是一个全球监管因素。
Shigella is an intracellular pathogen that primarily infects the human colon and causes shigellosis. Shigella virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master Shigella virulence regulator, is essential for the expression of T3SS-related genes. In this study, we found that
YhjC, a LysR-type transcriptional regulator, is required for Shigella virulence through activating the transcription of virF. Pathogenicity of the
yhjC mutant, including colonization in the colons of guinea pigs as well as its ability for host cell adhesion and invasion, was significantly lowered. Expression levels of virF and nearly all VirF-dependent genes were downregulated by yhjC deletion, indicating that
YhjC can activate virF transcription. Electrophoretic mobility shift assay analysis demonstrated that
YhjC could bind directly to the virF promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the virF expression and promotes Shigella virulence. Additionally, genome-wide expression analysis identified the presence of other genes in the large virulence plasmid and a genome exhibiting differential expression in response to yhjC deletion, with 169 downregulated and 99 upregulated genes, indicating that
YhjC also functioned as a global regulatory factor.