Resuscitation dynamics reveal persister partitioning after antibiotic treatment.
Resuscitation dynamics reveal persister partitioning after antibiotic treatment.
复制标题
DOI：
10.15252/msb.202211320
复制
发表时间：
2023-04-12
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
细菌可以通过形成休眠的耐药性坚持者而在抗生素中存活。Persisters可以复苏从休眠后治疗和延长感染。复苏被认为是随机发生的，但其短暂的单细胞性质使其难以调查。我们跟踪复苏的个别persisters氨苄青霉素治疗后，显微镜，并通过表征其动力学，发现大肠杆菌和沙门氏菌persisters复苏指数，而不是随机。我们证明了控制复苏的关键参数映射到治疗期间的氨苄青霉素浓度和复苏期间的外排。因此，我们观察到许多持续存在的后代具有指示细胞损伤的结构缺陷和转录反应，对于β-内酰胺和喹诺酮类抗生素。在复苏过程中，受损的存留细胞分配不均匀，产生健康的子细胞和有缺陷的子细胞。在肠道链球菌、肺炎克雷伯菌、铜绿假单胞菌和大肠杆菌尿路感染（UTI）分离株中观察到这种持久分配现象。在标准持久性试验中和临床UTI样品原位处理后也观察到了这种情况。这项研究揭示了复苏的新特性，并表明持久分配可能是缺乏遗传抗性的细菌的生存策略。跟踪和建模细菌持留菌的单细胞复苏动力学表明，这是一个药物依赖性和非随机过程。在抗生素治疗后，Persisters可以将细胞损伤划分为健康和不能存活的子细胞。
Bacteria can survive antibiotics by forming dormant, drug‐tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single‐cell nature makes it difficult to investigate. We tracked the resuscitation of individual persisters by microscopy after ampicillin treatment and, by characterizing their dynamics, discovered that Escherichia coli and Salmonella enterica persisters resuscitate exponentially rather than stochastically. We demonstrated that the key parameters controlling resuscitation map to the ampicillin concentration during treatment and efflux during resuscitation. Consistently, we observed many persister progeny have structural defects and transcriptional responses indicative of cellular damage, for both β‐lactam and quinolone antibiotics. During resuscitation, damaged persisters partition unevenly, generating both healthy daughter cells and defective ones. This persister partitioning phenomenon was observed in S. enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and an E. coli urinary tract infection (UTI) isolate. It was also observed in the standard persister assay and after in situ treatment of a clinical UTI sample. This study reveals novel properties of resuscitation and indicates that persister partitioning may be a survival strategy in bacteria that lack genetic resistance. Tracking and modelling single‐cell resuscitation dynamics of bacterial persisters shows that it is a drug‐dependent and non‐stochastic process. Persisters can partition cellular damage into healthy and nonviable daughter cells after antibiotic treatment.
影响因子：
3.6
作者：
Potluri LP;de Pedro MA;Young KD
通讯作者：
Young KD