Department of Microbiology, BMS Block, Panjab University, Chandigarh, 160014, India.
Inflammation. 2020 Dec;43(6):2344-2356. doi: 10.1007/s10753-020-01304-y.
Biofilms of Pseudomonas aeruginosa can cause complicated urinary tract infections especially in people with indwelling catheters which may result in pyelonephritis. Microorganisms in biofilm demonstrate high resistance to both antibiotics and host protection mechanisms, often resulting in chronic and difficult-to-treat infections. This study is aimed to assess in vivo and ex vivo efficacy of Zingerone nanoparticles (Z-NPs) against P. aeruginosa biofilm-associated murine acute pyelonephritis. In the present study, Zingerone and chitosan acted synergistically in the form of Z-NPs and found to be nontoxic to the kidney cell lines as depicted in MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay demonstrating their cytocompatibility. In vivo experiments indicated that Z-NPs (100 mg/kg) treatment reduced P. aeruginosa pathogenicity and enhanced the clearance of bacterial count from the renal and bladder tissue. Z-NPs improved the disease outcome by lowering the levels of various inflammatory markers, and histopathological examination revealed better recovery in renal and bladder tissue. Besides, ex vivo efficacy also confirmed that Z-NPs enhanced serum bactericidal effect along with increased phagocytic uptake and intracellular killing of P. aeruginosa as confirmed by fluorescent microscopy. To the best of our knowledge, this is the first study to provide evidence that Z-NPs are effective therapeutic agents for combating P. aeruginosa associated pyelonephritis.
铜绿假单胞菌生物膜可引起复杂的尿路感染，尤其是在留置导尿管的人群中，可能导致肾盂肾炎。生物膜中的微生物对抗生素和宿主保护机制具有高度抗性，常导致慢性和难以治疗的感染。本研究旨在评估荜澄茄酮纳米粒（Z-NPs）对铜绿假单胞菌生物膜相关鼠急性肾盂肾炎的体内和体外疗效。在本研究中，荜澄茄酮和壳聚糖以 Z-NPs 的形式协同作用，并且如 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐]测定所示对肾细胞系无毒性，表明其细胞相容性。体内实验表明，Z-NPs（100 mg/kg）治疗可降低铜绿假单胞菌的致病性，并从肾脏和膀胱组织中增强细菌计数的清除。Z-NPs 通过降低各种炎症标志物的水平改善疾病结局，组织病理学检查显示肾脏和膀胱组织的恢复更好。此外，体外疗效也证实，Z-NPs 增强了血清杀菌作用，同时通过荧光显微镜证实增加了对铜绿假单胞菌的吞噬摄取和细胞内杀伤。据我们所知，这是第一项证明 Z-NPs 是治疗铜绿假单胞菌相关肾盂肾炎的有效治疗剂的研究。
