铜绿假单胞菌是在免疫受损个体中引起急性和慢性感染的机会病原体。小调节RNA(sRNA)调节多种细菌对环境变化的适应,尤其是毒力.我们之前的研究表明,PrrHsRNA负调控许多毒力因子的表达,如青苷,鼠李糖脂,生物膜,和弹性蛋白酶在铜绿假单胞菌菌株PAO1中。然而,先前的研究表明,在急性小鼠肺部感染模型中,prrH缺陷型突变体可减弱毒力。所有感染ΔprrH的小鼠在整个28天的实验过程中都存活下来,而接种野生型或互补突变体的所有小鼠在注射后4天内都死于肺部感染,但具体机制尚不清楚。在这里,我们探讨了PrrH如何通过调节毒力因子的表达介导严重肺损伤。小鼠体内和体外细胞实验表明,PrrH增强了PAO1的致病性,引起严重的肺损伤。机械上,PrrH与exsAmRNA的编码序列区结合,编码III型分泌系统主调节蛋白。我们进一步证明了PrrH介导了严重的炎症反应并加剧了A549细胞的凋亡。总的来说,我们的结果表明,PrrH正调节ExsA,增强铜绿假单胞菌的致病性,导致严重的肺损伤.重要铜绿假单胞菌是革兰氏阴性细菌,是医院获得性肺炎的主要原因。铜绿假单胞菌的致病性是由于许多毒力因子的分泌。小调节RNA(sRNA)调节各种细菌适应,尤其是毒力.因此,了解sRNA调节毒力的机制对于了解铜绿假单胞菌的致病性和相关疾病的治疗是必要的。在这项研究中,我们证明了PrrH通过与ExsA的编码序列区结合增强铜绿假单胞菌的致病性,III型分泌系统的主要调节蛋白,引起严重的肺损伤,加剧炎症反应和细胞凋亡。这些发现表明,PrrH是一种积极调节ExsA的关键分子。在临床实践中,III型阳性菌株通常与铜绿假单胞菌感染的高死亡率相关。因此,这一发现可能为治疗铜绿假单胞菌感染提供新的靶点,尤其是III型阳性菌株.
Pseudomonas aeruginosa is an opportunistic pathogen that causes acute and chronic infections in immunocompromised individuals. Small regulatory RNAs (sRNAs) regulate multiple bacterial adaptations to environmental changes, especially virulence. Our previous study showed that sRNA PrrH negatively regulates the expression of a number of virulence factors, such as pyocyanin, rhamnolipid, biofilm, and elastase in the P. aeruginosa strain PAO1. However, previous studies have shown that the prrH-deficient mutant attenuates virulence in an acute murine lung infection model. All ΔprrH-infected mice survived the entire 28-day course of the experiment, whereas all mice inoculated with the wild-type or the complemented mutant succumbed to lung infection within 4 days of injection, but the specific mechanism is unclear. Herein, we explored how PrrH mediates severe lung injury by regulating the expression of virulence factors. In vivo mouse and in vitro cellular assays demonstrated that PrrH enhanced the pathogenicity of PAO1, causing severe lung injury. Mechanistically, PrrH binds to the coding sequence region of the mRNA of exsA, which encodes the type III secretion system master regulatory protein. We further demonstrated that PrrH mediates a severe inflammatory response and exacerbates the apoptosis of A549 cells. Overall, our results revealed that PrrH positively regulates ExsA, enhances the pathogenicity of P. aeruginosa, and causes severe lung injury.
OBJECTIVE: Pseudomonas aeruginosa is a Gram-negative bacterium and the leading cause of nosocomial pneumonia. The pathogenicity of P. aeruginosa is due to the secretion of many virulence factors. Small regulatory RNAs (sRNAs) regulate various bacterial adaptations, especially virulence. Therefore, understanding the mechanism by which sRNAs regulate virulence is necessary for understanding the pathogenicity of P. aeruginosa and the treatment of the related disease. In this study, we demonstrated that PrrH enhances the pathogenicity of P. aeruginosa by binding to the coding sequence regions of the ExsA, the master regulatory protein of type III secretion system, causing severe lung injury and exacerbating the inflammatory response and apoptosis. These findings revealed that PrrH is a crucial molecule that positively regulates ExsA. Type III-positive strains are often associated with a high mortality rate in P. aeruginosa infections in clinical practice. Therefore, this discovery may provide a new target for treating P. aeruginosa infections, especially type III-positive strains.