Department of Biology, Faculty of Science, Hacettepe University, Ankara, Turkey.
Genetica. 2021 Feb;149(1):73-80. doi: 10.1007/s10709-021-00114-w. Epub 2021 Jan 27.
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相互作用并塑造全基因组突变率和突变谱非常重要。在这里，我们使用结合了重复系全基因组重测序的突变积累设计，对大肠杆菌在长期亚抑菌浓度暴露于广谱（链霉素）和窄谱（萘啶酸）抗生素后的全基因组突变谱进行了定量评估，以此作为诱变试验。我们发现，虽然与对照相比，链霉素处理组的全基因组突变率略高，但在萘啶酸处理组中显著增加。我们的研究结果表明，广谱和窄谱抗生素都可能提高大肠杆菌的突变率，但作用机制可能会影响后果，从而加速适应速度并赋予抗生素耐药性。
