BACKGROUND The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin. It is currently unknown whether l-serine affects other type of antibiotics such as β-lactams and fluoroquinolones. METHODS Using E. coli, we studied the combination of l-serine with diverse antibiotics against laboratory and clinical E. coli cultures and persisters. The intracellular NAD(+)/NADH level and ROS were determined using kits. Total cellular iron was determined by using a colorimetric ferrozine-based assay. RESULTS Exogenous l-serine sensitized E. coli ATCC 25922 and clinically isolated fluoroquinolone-resistant E. coli to fluoroquinolones. This potentiation is independent of growth phase. Addition of serine increases the production of NADH. The underlying mechanism of this strategy is that the combination of serine with ofloxacin or moxifloxacin increases the NAD(+)/NADH ratio, disrupts the Fe-S clusters and increases the production of endogenous reactive oxygen species. Furthermore, we used a serine and ofloxacin or moxifloxacin combination in vitro to combat bacterial persister cells, compared with antibiotic treatment alone; combinational treatments of persister cells with antibiotics and l-serine resulted in a significantly greater decrease in cell viability. CONCLUSIONS To our knowledge, this is the first report that l-serine can potentiate the action of ofloxacin or moxifloxacin against Gram-negative bacteria and could constitute a new strategy for the eradication of bacterial infections.

中文翻译：

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l-丝氨酸通过增强内源性活性氧的产生来增强氟喹诺酮对大肠杆菌的活性。

背景技术多种抗微生物细菌的增加严重威胁全球公共健康。迫切需要新颖有效的策略。据报道，l-丝氨酸是对抗细菌生长的最有效的氨基酸抑制剂，可以使大肠杆菌细胞对庆大霉素敏感。目前尚不清楚L-丝氨酸是否会影响其他类型的抗生素，例如β-内酰胺类和氟喹诺酮类。方法使用大肠杆菌，我们研究了L-丝氨酸与多种抗生素的结合，以针对实验室和临床大肠杆菌培养物和持久性。使用试剂盒测定细胞内NAD（+）/ NADH水平和ROS。总细胞铁含量是通过使用比色铁基比色法测定的。结果外源的l-丝氨酸致敏的大肠杆菌ATCC 25922和临床分离的对氟喹诺酮类耐药的大肠杆菌。大肠杆菌转化为氟喹诺酮类药物。这种增强作用与生长阶段无关。丝氨酸的添加增加了NADH的产生。该策略的潜在机制是丝氨酸与氧氟沙星或莫西沙星的组合增加NAD（+）/ NADH比率，破坏Fe-S团簇并增加内源性活性氧的产生。此外，与单独的抗生素治疗相比，我们在体外使用了丝氨酸和氧氟沙星或莫西沙星的组合来对抗细菌性持久性细胞。持久性细胞与抗生素和l-丝氨酸的联合治疗导致细胞活力的下降幅度更大。结论据我们所知，