PDF(Pubmed)
Abstract：
Shigella causes shigellosis that requires antibiotic treatment in severe cases. Sublethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unclear. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a NOR-sensitive strain, Shigella sonnei UKMCC1015. Firstly, the whole genome of S. sonnei UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. Interestingly, transcriptomic analysis showed that low NOR levels do not change either the expression of the AMR genes or NOR targets such as gyrA. Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated guanosine pentaphosphate and tetraphosphate (ppGpp) levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase (relA). Additionally, we observed that a relA overexpression (prolonged period of elevated ppGpp levels) may negatively affect the NOR tolerance of the bacteria. In conclusion, this study revealed that a NOR-sensitive strain responds differently to sublethal NOR than commonly reported in resistant strains.
摘要：
志贺氏菌引起志贺氏菌病，在严重的情况下需要抗生素治疗。亚致死抗生素浓度可以促进耐药性，但它们在耐药性发展之前对抗生素敏感细菌的影响尚不清楚。这项研究调查了亚致死诺氟沙星（NOR）挑战对NOR敏感菌株的影响，志贺氏菌unneiUKMCC1015。首先,组装了S.sonneiUKMCC1015的整个基因组，并鉴定了45个抗菌素耐药性（AMR）基因。有趣的是,转录组学分析显示，低NOR水平不会改变AMR基因或NOR靶标如gyrA的表达。相反，多个核糖体蛋白基因下调，这可能归因于核糖体蛋白启动子活性降低，由升高的五磷酸鸟苷和四磷酸鸟苷（ppGpp）水平调节。该警报涉及环境胁迫期间的细菌严格反应，它主要由ppGpp合成酶（relA）产生。此外,我们观察到relA过表达（ppGpp水平升高的时间延长）可能会对细菌的NOR耐受性产生负面影响。总之,这项研究表明，NOR敏感菌株对亚致死NOR的反应与耐药菌株中通常报道的不同。
