UvrY is required for the full virulence of <i>Aeromonas dhakensis</i>

<i>Aeromonas dhakensis</i> is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against <i>A. dhakensis</i> infection is urgent. To understand its pathogenesis, we created an <i>A. dhakensis</i> AAK1 mini-Tn10 transposon library to study the mechanism of <i>A. dhakensis</i> infection. By using a <i>Caenorhabditis elegans</i> model, we established a screening platform for the purpose of identifying attenuated mutants. The <i>uvrY</i> mutant, which conferred the most attenuated toxicity toward <i>C. elegans</i>, was identified. The <i>uvrY</i> mutant was also less virulent in C2C12 fibroblast and mice models, in line with <i>in vitro</i> results. To further elucidate the mechanism of UvrY in controlling the toxicity in <i>A. dhakensis</i>, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin <i>ahh1</i> and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of <i>uvrY</i> mutant in <i>C. elegans</i>; however, complementation of <i>ahh1</i> endogenous promoter-driven <i>ahh1</i> could not produce Ahh1 and rescue the virulence in the <i>uvrY</i> mutant. These findings suggest that UvrY is required for the expression of Ahh1 in <i>A. dhakensis</i>. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of <i>A. dhakensis</i>. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.