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

中文翻译：

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UvrY是dhakensis气单胞菌完全毒力所必需的。

达克气单胞菌是一种新兴的人类病原体，在世界范围内引起快速和严重的感染。在缺乏有用抗生素的压力下，迫切需要找到一种新的策略来应对达克曲霉。为了了解其发病机理，我们创建了一个dh.dhakensis AAK1 mini-Tn10转座子文库，以研究dh。dhakensis感染的机制。通过使用秀丽隐杆线虫模型，我们建立了一个筛选平台，用于鉴定减毒突变体。鉴定了uvrY突变体，该突变体对秀丽隐杆线虫具有最弱的毒性。uvrY突变体在C2C12成纤维细胞和小鼠模型中的毒性也较低，与体外结果一致。为了进一步阐明UvrY在控制dh.dhakensis中毒性的机制，我们进行了转录组分析。RNAseq结果表明，独特的溶血素ahh1和其他毒力因子的表达受UvrY调控。补充最重要的毒力因子之一的Ahh1，拯救了秀丽隐杆线虫uvrY突变体的孔形成表型。但是，ahh1内源性启动子驱动的ahh1的互补不能产生Ahh1，也不能挽救uvrY突变体中的毒力。这些发现表明，UvrY是在dhakensis中表达Ahh1所必需的。两者合计，我们的结果表明，UvrY控制几种不同的毒力因子，是达克拟南芥完全毒力所必需的。因此，双组分调节剂UvrY是潜在的治疗靶标，值得进一步研究。最重要的毒力因子之一，挽救了秀丽隐杆线虫uvrY突变体的孔形成表型。但是，ahh1内源性启动子驱动的ahh1的互补不能产生Ahh1，也不能挽救uvrY突变体中的毒力。这些发现表明，UvrY是Ahh1在dhakensis中表达所必需的。两者合计，我们的结果表明，UvrY控制几种不同的毒力因子，是达克拟南芥完全毒力所必需的。因此，双组分调节剂UvrY是潜在的治疗靶标，值得进一步研究。最重要的毒力因子之一，挽救了秀丽隐杆线虫uvrY突变体的孔形成表型。但是，ahh1内源性启动子驱动的ahh1的互补不能产生Ahh1，也不能拯救uvrY突变体中的毒力。这些发现表明，UvrY是在dhakensis中表达Ahh1所必需的。两者合计，我们的结果表明，UvrY控制几种不同的毒力因子，是达克拟南芥完全毒力所必需的。因此，双组分调节剂UvrY是潜在的治疗靶标，值得进一步研究。这些发现表明，UvrY是在dhakensis中表达Ahh1所必需的。两者合计，我们的结果表明，UvrY控制几种不同的毒力因子，是达克拟南芥完全毒力所必需的。因此，双组分调节剂UvrY是潜在的治疗靶标，值得进一步研究。这些发现表明，UvrY是在dhakensis中表达Ahh1所必需的。两者合计，我们的结果表明，UvrY控制几种不同的毒力因子，是达克拟南芥完全毒力所必需的。因此，双组分调节剂UvrY是潜在的治疗靶标，值得进一步研究。