Since antibiotic resistance is a growing public health problem worldwide, it is important to understand how antibiotics and spontaneous mutations cooperate and shape the genome-wide mutation rate and spectrum. Here, we quantitatively evaluate genome-wide mutational profiles of Escherichia coli after long-term subinhibitory exposure to a broad-spectrum (streptomycin) and a narrow-spectrum antibiotic (nalidixic acid), using a mutation accumulation design combined with whole-genome resequencing of replicate lines as a mutagenicity test. We determined that, while the genome-wide mutation rate is slightly higher in the streptomycin-treated lines compared to the control lines, there is a significant increase in the nalidixic acid-treated lines. Our findings suggest that both broad and narrow-spectrum antibiotics may elevate the mutation rates in E. coli, but mechanisms of action may affect the consequence, thus contribute to accelerating the rate of adaptation and conferring antibiotic resistance.

由于抗生素耐药性是全球范围内日益严重的公共卫生问题，因此了解抗生素和自发突变如何协同作用并影响全基因组突变率和光谱至关重要。在这里，我们定量评估大肠杆菌的全基因组突变概况长期亚抑制长期暴露于广谱（链霉素）和窄谱抗生素（纳洛地酸）后，使用突变积累设计结合复制系的全基因组重测序作为诱变性测试。我们确定，尽管链霉素处理的品系的全基因组突变率比对照品系略高，但萘啶酸处理的品系却显着增加。我们的发现表明，广谱和窄谱抗生素均可提高大肠杆菌的突变率，但作用机制可能会影响其结果，从而有助于加快适应率并赋予抗生素抗性。