YhjC is a novel transcriptional regulator required for Shigella flexneri virulence

<i>Shigella</i> is an intracellular pathogen that primarily infects the human colon and causes shigellosis. <i>Shigella</i> virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master <i>Shigella</i> 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 <i>Shigella</i> virulence through activating the transcription of <i>virF</i>. Pathogenicity of the <i>yhjC</i> 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 <i>virF</i> and nearly all VirF-dependent genes were downregulated by <i>yhjC</i> deletion, indicating that YhjC can activate <i>virF</i> transcription. Electrophoretic mobility shift assay analysis demonstrated that YhjC could bind directly to the <i>virF</i> promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the <i>virF</i> expression and promotes <i>Shigella</i> 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 <i>yhjC</i> deletion, with 169 downregulated and 99 upregulated genes, indicating that YhjC also functioned as a global regulatory factor.