Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an 710061, P.R. China.
J Microbiol Biotechnol. 2021 Sep 28;31(9):1200-1209. doi: 10.4014/jmb.2105.05024.
Sepsis is an acute inflammatory response that leads to life-threatening complications if not quickly and adequately treated. Cytolysin, hemolysin, and pneumolysin are toxins produced by gram-positive bacteria and are responsible for resistance to antimicrobial drugs, cause virulence and lead to sepsis. This work assessed the effects of aloe-emodin (AE) and photodynamic therapy (PDT) on sepsis-associated gram-positive bacterial toxins. Standard and antibiotic-resistant , , and bacterial strains were cultured in the dark with varying AE concentrations and later irradiated with 72 J/cm light. Colony and biofilm formation was determined. CCK-8, Griess reagent reaction, and ELISA assays were done on bacteria-infected RAW264.7 cells to determine the cell viability, NO, and IL-1β and IL-6 pro-inflammatory cytokines responses, respectively. Hemolysis and western blot assays were done to determine the effect of treatment on hemolysis activity and sepsis-associated toxins expressions. AE-mediated PDT reduced bacterial survival in a dose-dependent manner with 32 μg/ml of AE almost eliminating their survival. Cell proliferation, NO, IL-1β, and IL-6 cytokines production were also significantly downregulated. Further, the hemolytic activities and expressions of cytolysin, hemolysin, and pneumolysin were significantly reduced following AE-mediated PDT. In conclusion, combined use of AE and light (435 ± 10 nm) inactivates MRSA, (ATCC 29213), (ATCC 49619), MDR-, (ATCC 29212), and VRE (ATCC 51299) in an AE-dose dependent manner. AE and light are also effective in reducing biofilm formations, suppressing pro-inflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.
脓毒症是一种急性炎症反应,如果不能迅速和充分地治疗,可能会导致危及生命的并发症。细胞溶解素、溶血素和肺炎球菌溶血素是革兰氏阳性菌产生的毒素,它们对抗生素耐药,导致毒力并导致脓毒症。本研究评估了大黄素(AE)和光动力疗法(PDT)对脓毒症相关革兰氏阳性菌毒素的影响。标准和抗生素耐药的 、 、 和 细菌菌株在黑暗中用不同浓度的 AE 培养,然后用 72 J/cm 的光照射。测定菌落和生物膜形成。用 CCK-8、Griess 试剂反应和 ELISA 检测法分别在细菌感染的 RAW264.7 细胞上检测细胞活力、NO 和促炎细胞因子 IL-1β和 IL-6 的反应。进行溶血和 Western blot 测定以确定治疗对溶血活性和脓毒症相关毒素表达的影响。AE 介导的 PDT 以剂量依赖性方式降低细菌存活率,32μg/ml 的 AE 几乎消除了其存活率。细胞增殖、NO、IL-1β和 IL-6 细胞因子的产生也显著下调。此外,AE 介导的 PDT 后细胞溶解素、溶血素和肺炎球菌溶血素的溶血活性和表达也显著降低。总之,AE 和光(435±10nm)的联合使用以 AE 剂量依赖性方式使 MRSA、 (ATCC 29213)、 (ATCC 49619)、MDR-、 (ATCC 29212)和 VRE(ATCC 51299)失活。AE 和光也可有效减少生物膜形成,抑制促炎细胞因子、溶血活性,并抑制引起脓毒症的毒素表达。