Single-cell imaging and characterization of Escherichia coli persister cells to ofloxacin in exponential cultures
Single-cell imaging and characterization of Escherichia coli persister cells to ofloxacin in exponential cultures
复制标题
DOI：
10.1126/sciadv.aav9462
复制
发表时间：
2019-06-01
期刊：
影响因子：
13.6
通讯作者：
Van Melderen, Laurence
中科院分区：
文献类型：
--
作者：
Goormaghtigh, Frederic;Van Melderen, Laurence
细菌持久性是指克隆群体中小亚群体耐受抗生素的能力。持久性细菌被认为起源于休眠细胞，在休眠细胞中，抗生素靶点活性较低，不能被破坏。在这里，我们报告了在指数增长的培养中，氧氟沙星持久体起源于代谢活跃的细胞：这些细胞在添加氧氟沙星之前就开始分裂，并且在治疗期间确实遭受DNA损伤，类似于它们的非持久体兄弟姐妹。我们观察到，在大多数种群中，生长速度、DNA含量和SOS诱导在持久性中各不相同，因此不能构成持久性的预测标记。在去除氧氟沙星后，持久性细胞通常形成长多核丝，并达到最大的SOS诱导。最终，细胞继续分裂，产生新的种群。我们的研究结果强调了持久性细胞的异质性，因此需要在单细胞水平上逐个分析这些低频表型变异。
Bacterial persistence refers to the capacity of small subpopulations within clonal populations to tolerate antibiotics. Persisters are thought to originate from dormant cells in which antibiotic targets are less active and cannot be corrupted. Here, we report that in exponentially growing cultures, ofloxacin persisters originate from metabolically active cells: These cells are dividing before the addition of ofloxacin and do endure DNA damages during the treatment, similar to their nonpersister siblings. We observed that growth rate, DNA content, and SOS induction vary among persisters, as in the bulk of the population and therefore do not constitute predictive markers for persistence. Persister cells typically form long polynucleoid filaments and reach maximum SOS induction after removal of ofloxacin. Eventually, cell division resumes, giving rise to a new population. Our findings highlight the heterogeneity of persister cells and therefore the need to analyze these low-frequency phenotypic variants on a case-by-case basis at the single-cell level.