■铜绿假单胞菌是一种普遍存在的病原体,通过调节群体感应(QS)引起各种传染病。干扰铜绿假单胞菌QS系统的策略,加上常规抗生素的剂量减少,提出了治疗感染和减轻抗生素耐药性的潜在解决方案。在这项研究中,合成了7种肉桂酰基异羟肟酸盐,以评估其对铜绿假单胞菌QS的抑制作用。在这些肉桂酸衍生物中,我们发现肉桂酰基异羟肟酸(CHA)和3-甲氧基-肉桂酰基异羟肟酸(MCHA)是两种最有效的候选药物。更进一步,评价CHA和MCHA对铜绿假单胞菌产生毒力因子和生物膜的影响。最终,我们的研究可能为治疗铜绿假单胞菌感染和降低其毒力提供有希望的潜力.
■进行圆盘扩散测试以评估对7种肉桂酰基异羟肟酸盐的QS的抑制作用。进一步探讨了CHA和MCHA对铜绿假单胞菌产生毒力和鞭毛运动的影响。采用扫描电镜(SEM)实验评价CHA和MCHA对铜绿假单胞菌生物膜形成的抑制作用。RT-qPCR用于检测rhlI,拉萨,LasB,rhla,rhlB,铜绿假单胞菌中的oprL基因。进行了计算机对接研究,以探索CHA和MCHA的分子机制。检测到CHA与庆大霉素对生物膜细胞分散的协同作用。
■CHA或MCHA治疗后,多种毒力因子的产生,包括绿脓苷,蛋白酶,鼠李糖脂,和铁载体,铜绿假单胞菌游泳和成群活动受到显著抑制。我们的结果表明CHA和MCHA可以消除铜绿假单胞菌形成的生物膜。RT-qPCR显示CHA和MCHA抑制铜绿假单胞菌QS相关基因的表达。分子对接表明CHA和MCHA主要通过与同源信号分子C4-HSL竞争来抑制铜绿假单胞菌中的RhlI/R系统。此外,CHA与庆大霉素对生物膜细胞分散表现出有效的协同作用。
■P.铜绿假单胞菌是临床和流行病学上最重要的细菌之一,也是导尿管相关尿路感染和呼吸机相关肺炎的主要原因。本研究旨在探讨肉桂酰基异羟肟酸盐对QS的抑制作用。我们的结果表明,CHA和MCHA,作为两个小说QSI,为治疗铜绿假单胞菌感染和降低其毒力提供了有希望的潜力。
UNASSIGNED: Pseudomonas aeruginosa is a ubiquitous pathogen that causes various infectious diseases through the regulation of quorum sensing (QS). The strategy of interfering with the QS systems of P. aeruginosa, coupled with a reduction in the dosage of conventional antibiotics, presents a potential solution to treating infection and mitigating antibiotic resistance. In this study, seven cinnamoyl hydroxamates were synthesized to evaluate their inhibitory effects on QS of P. aeruginosa. Among these cinnamic acid derivatives, we found cinnamoyl hydroxamic acid (CHA) and 3-methoxy-cinnamoyl hydroxamic acid (MCHA) were the two most effective candidates. Furtherly, the effect of CHA and MCHA on the production of virulence factors and biofilm of P. aeruginosa were evaluated. Ultimately, our study may offer promising potential for treating P. aeruginosa infections and reducing its virulence.
UNASSIGNED: The disc diffusion test were conducted to evaluate inhibitory effects on QS of seven cinnamoyl hydroxamates. The influence of CHA and MCHA on the production of virulence and flagellar motility of P. aeruginosa was furtherly explored. Scanning electron microscopy (SEM) experiment were conducted to evaluate the suppression of CHA and MCHA on the formed biofilm of P. aeruginosa. RT-qPCR was used to detect rhlI, lasA, lasB, rhlA, rhlB, and oprL genes in P. aeruginosa. In silico docking study was performed to explore the molecular mechanism of CHA and MCHA. The synergistic effects of CHA with
gentamicin were detected on biofilm cell dispersal.
UNASSIGNED: After treatment of CHA or MCHA, the production of multiple virulence factors, including pyocyanin, proteases, rhamnolipid, and siderophore, and swimming and swarming motilities in P. aeruginosa were inhibited significantly. And our results showed CHA and MCHA could eliminate the formed biofilm of P. aeruginosa. RT-qPCR revealed that CHA and MCHA inhibited the expression of QS related genes in P. aeruginosa. Molecular docking indicated that CHA and MCHA primarily inhibited the RhlI/R system in P. aeruginosa by competing with the cognate signaling molecule C4-HSL.Additionally, CHA exhibited potent synergistic effects with
gentamicin on biofilm cell dispersal.
UNASSIGNED: P. aeruginosa is one of the most clinically and epidemiologically important bacteria and a primary cause of catheter-related urinary tract infections and ventilator-associated pneumonia. This study aims to explore whether cinnamoyl hydroxamates have inhibitory effects on QS. And our results indicate that CHA and MCHA, as two novel QSIs, offer promising potential for treating P. aeruginosa infections and reducing its virulence.