Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Curr Microbiol. 2020 Mar;77(3):479-490. doi: 10.1007/s00284-019-01858-7. Epub 2020 Jan 7.
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in humans, notably cystic fibrosis. P. aeruginosa faces various stresses such as oxidative stress either in the environment or within the host during infection. In the present study, the influence of oxidative stress on both Pseudomonas antibiotic susceptibility and host pathogenesis was characterized. Prior exposure to HO significantly altered P. aeruginosa susceptibility to tested antibiotics; colistin, ciprofloxacin, tobramycin, and ceftazidime. The minimum inhibitory concentrations (MICs) of tested antibiotics either increased or decreased following HO exposure. Importantly, RT-qPCR revealed that expression of quorum sensing genes, that regulate virulence factors production in P. aeruginosa, was significantly higher in unstressed relative to HO-stressed cells. The impact of P. aeruginosa exposure to oxidative stress by HO on bacterial pathogenesis was investigated using in vivo mice infection model. Interestingly, exposure to oxidative stress markedly reduces P. aeruginosa pathogenesis in mice. Unstressed P. aeruginosa was able to kill more mice as compared to HO-stressed bacteria. In addition, body weight of mice infected with unstressed P. aeruginosa was lower than that of mice inoculated with stressed bacteria. Isolated organs (spleen, liver, and kidney) from mice infected with unstressed bacteria exhibited increased weight as well as bacterial load in comparison with mice infected with stressed bacteria. In summary, current data highlight the impact of oxidative stress on P. aeruginosa antibiotic susceptibility as well as host pathogenesis. These findings could be helpful in treatment of infections caused by this important pathogen.
铜绿假单胞菌是一种革兰氏阴性机会性病原体，可导致人类发生严重感染，尤其是囊性纤维化。铜绿假单胞菌在环境中或感染宿主时会面临各种压力，如氧化应激。在本研究中，我们研究了氧化应激对铜绿假单胞菌抗生素敏感性和宿主发病机制的影响。先前暴露于 H2O2 显著改变了铜绿假单胞菌对测试抗生素的敏感性；多粘菌素、环丙沙星、妥布霉素和头孢他啶。测试抗生素的最小抑菌浓度（MIC）在 H2O2 暴露后要么增加，要么减少。重要的是，RT-qPCR 显示，调节铜绿假单胞菌毒力因子产生的群体感应基因的表达在未应激细胞中明显高于 H2O2 应激细胞。通过 H2O2 暴露研究了铜绿假单胞菌暴露于氧化应激对细菌发病机制的影响，使用体内小鼠感染模型。有趣的是，暴露于氧化应激可显著降低铜绿假单胞菌在小鼠中的发病机制。未应激的铜绿假单胞菌比 H2O2 应激细菌更能杀死更多的小鼠。此外，感染未应激铜绿假单胞菌的小鼠的体重低于感染应激细菌的小鼠。与感染应激细菌的小鼠相比，感染未应激细菌的小鼠分离的器官（脾脏、肝脏和肾脏）的重量以及细菌载量增加。总之，目前的数据强调了氧化应激对铜绿假单胞菌抗生素敏感性以及宿主发病机制的影响。这些发现可能有助于治疗这种重要病原体引起的感染。
