Wong Bao Chi, Law Soffi Kei Kei, Md Zoqratt Muhammad Zarul Hanifah, Ayub Qasim, Tan Hock Siew
School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
Monash University Malaysia Genomics Platform, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
R Soc Open Sci. 2024 Jun 19;11(6):232025. doi: 10.1098/rsos.232025. eCollection 2024 Jun.
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, UKMCC1015. Firstly, the whole genome of 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 . 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 (). Additionally, we observed that a 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.
引起志贺氏菌病，严重病例需要抗生素治疗。亚致死浓度的抗生素会促进耐药性，但它们在耐药性产生之前对抗生素敏感细菌的影响尚不清楚。本研究调查了亚致死浓度的诺氟沙星（NOR）对NOR敏感菌株UKMCC1015的影响。首先，组装了UKMCC1015的全基因组，并鉴定出45个抗菌抗性（AMR）基因。有趣的是，转录组分析表明，低NOR水平既不会改变AMR基因的表达，也不会改变NOR靶点的表达。相反，多个核糖体蛋白基因被下调，这可能归因于核糖体蛋白启动子活性的降低，这是由鸟苷五磷酸和四磷酸（ppGpp）水平升高调节的。这种警报素参与环境压力下的细菌严谨反应，它主要由ppGpp合成酶产生。此外，我们观察到ppGpp过表达（ppGpp水平长时间升高）可能会对细菌的NOR耐受性产生负面影响。总之，本研究表明，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。
