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Ciprofloxacin interferes with Salmonella Typhimurium intracellular survival and host virulence through repression of Salmonella pathogenicity island-2 (SPI-2) genes expression.
Pathogens and Disease ( IF 3.3 ) Pub Date : 2020-02-21 , DOI: 10.1093/femspd/ftaa011
Momen Askoura 1 , Wael Abdel Halim Hegazy 1, 2
Affiliation  

Current study aims to characterize influence of sub-minimum inhibitory concentration (sub-MIC) of ciprofloxacin on Salmonella intracellular survival and host virulence. Herein, Salmonella resistance patterns to various antibiotics were in agreement with those reported in previous studies. Moreover, intracellular survival of both ciprofloxacin-sensitive and -resistant Salmonella was markedly reduced upon treatment with sub-MIC of ciprofloxacin as determined by gentamicin protection assay. These findings were further confirmed using immunostaining indicating an inhibitory effect of sub-MIC of ciprofloxacin on Salmonella intracellular survival. RT-qPCR revealed that expression of genes encoding Salmonella type three secretion system (TTSS) decreased upon bacterial exposure to sub-MIC of ciprofloxacin. Furthermore, bacterial exposure to sub-MIC of ciprofloxacin significantly reduced expression of both sifA and sifB, which are important for Salmonella filaments formation within host. Treatment of Salmonella with sub-MIC of ciprofloxacin reduced bacterial capacity to kill mice infection models. A lower mortality rate was observed in mice injected with Salmonella treated with sub-MIC of ciprofloxacin as compared to mice inoculated with untreated bacteria. Collectively, current findings indicate that, in addition to its bactericidal potential, sub-MIC of ciprofloxacin could inhibit Salmonella intracellular survival, virulence genes expression as well as host pathogenesis, providing another mechanism for ciprofloxacin in limiting Salmonella host infection.

中文翻译:

环丙沙星通过抑制沙门氏菌致病岛2(SPI-2)基因表达来干扰鼠伤寒沙门氏菌细胞内存活和宿主毒力。

当前的研究旨在表征环丙沙星的亚最低抑制浓度(sub-MIC)对沙门氏菌细胞内存活和宿主毒力的影响。在本文中,沙门氏菌对各种抗生素的耐药模式与先前研究中报道的一致。此外,如由庆大霉素保护试验所测定,用环丙沙星的亚MIC治疗后,环丙沙星敏感和耐药沙门氏菌的细胞内存活率均显着降低。使用免疫染色进一步证实了这些发现,表明环丙沙星的亚MIC对沙门氏菌细胞内存活具有抑制作用。RT-qPCR显示,细菌暴露于环丙沙星的亚MIC后,编码三型沙门氏菌分泌系统(TTSS)的基因表达降低。此外,细菌暴露于环丙沙星的MIC之下会显着降低sifA和sifB的表达,这对于宿主内沙门氏菌细丝的形成非常重要。用环丙沙星亚MIC治疗沙门氏菌会降低杀死小鼠感染模型的细菌能力。与未接种细菌的小鼠相比,在用环丙沙星亚MIC治疗的沙门氏菌注射的小鼠中观察到较低的死亡率。总的来说,当前的发现表明,环丙沙星的亚MIC除了具有杀菌潜力外,还可以抑制沙门氏菌的细胞内存活,毒力基因表达以及宿主发病机制,为环丙沙星限制沙门氏菌宿主感染提供了另一种机制。这对于宿主内沙门氏菌细丝的形成很重要。用环丙沙星亚MIC治疗沙门氏菌会降低杀死小鼠感染模型的细菌能力。与未接种细菌的小鼠相比,在用环丙沙星亚MIC治疗的沙门氏菌注射的小鼠中观察到较低的死亡率。总的来说,当前的发现表明,环丙沙星的亚MIC除了具有杀菌潜力外,还可以抑制沙门氏菌的细胞内存活,毒力基因表达以及宿主发病机制,为环丙沙星限制沙门氏菌宿主感染提供了另一种机制。这对于宿主内沙门氏菌细丝的形成很重要。用环丙沙星亚MIC治疗沙门氏菌会降低杀死小鼠感染模型的细菌能力。与未接种细菌的小鼠相比,在用环丙沙星亚MIC治疗的沙门氏菌注射的小鼠中观察到较低的死亡率。总的来说,当前的发现表明,环丙沙星的亚MIC除了具有杀菌潜力外,还可以抑制沙门氏菌的细胞内存活,毒力基因表达以及宿主发病机制,为环丙沙星在限制沙门氏菌宿主感染中提供了另一种机制。与未接种细菌的小鼠相比,在用环丙沙星亚MIC治疗的沙门氏菌注射的小鼠中观察到较低的死亡率。总的来说,当前的发现表明,环丙沙星的亚MIC除了具有杀菌潜力外,还可以抑制沙门氏菌的细胞内存活,毒力基因表达以及宿主发病机制,为环丙沙星在限制沙门氏菌宿主感染中提供了另一种机制。与未接种细菌的小鼠相比,用环丙沙星亚MIC治疗的沙门氏菌注射的小鼠死亡率更低。总的来说,当前的发现表明,环丙沙星的亚MIC除了具有杀菌潜力外,还可以抑制沙门氏菌的细胞内存活,毒力基因表达以及宿主发病机制,为环丙沙星在限制沙门氏菌宿主感染中提供了另一种机制。
更新日期:2020-04-01
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