Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Frederiksberg C, Denmark.
Microbial Pathogenesis and Host Susceptibility, Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 København S, Denmark.
Microbiology (Reading). 2020 Jul;166(7):654-658. doi: 10.1099/mic.0.000926.
Bacterial persisters form a subpopulation of cells that survive lethal concentrations of antibiotics without being genetically different from the susceptible population. They are generally considered to be phenotypic variants that spontaneously have entered a dormant state with low ATP levels or reduced membrane potential. In , a serious opportunistic human pathogen, persisters are believed to contribute to chronic infections that are a major global healthcare problem. While persisters have mostly been studied in laboratory strains, we have here investigated the ability of clinical strains to form persisters. For 44 clinical strains belonging to the major clonal complexes CC5, CC8, CC30 or CC45, we examined persister cell formation in stationary phase when exposed to 100 times the MIC of ciprofloxacin, an antibiotic that targets DNA replication. We find that while all strains are able to form persisters, those belonging to CC30 displayed on average 100-fold higher persister cell frequencies when compared to strains of other CCs. Importantly, there was no correlation between persister formation and the cellular ATP content of the individual strains, but the group of CC30 strains displayed slightly lower membrane potential compared to the non-CC30 group. CC30 strains have previously been associated with chronic and reoccuring infections and we hypothesize that there could be a correlation between lineage-specific characteristics displayed via persister assays and the observed clinical spectrum of disease.
细菌持久型是指在抗生素致死浓度下存活而与敏感群体在遗传上没有差异的细胞亚群。它们通常被认为是表型变体，会自发进入休眠状态，此时细胞内 ATP 水平较低或膜电位降低。在 中，持久型被认为是导致慢性感染的原因之一，慢性感染是一个全球性的主要医疗保健问题。虽然持久型主要在实验室菌株中进行研究，但我们在此研究了临床菌株形成持久型的能力。对于属于主要克隆复合体 CC5、CC8、CC30 或 CC45 的 44 株临床菌株，我们在暴露于环丙沙星（一种针对 DNA 复制的抗生素）MIC100 倍的静止期时，检查了持久型细胞的形成。我们发现，虽然所有菌株都能够形成持久型，但与其他 CC 的菌株相比，属于 CC30 的菌株形成持久型细胞的频率平均高出 100 倍。重要的是，持久型形成与个体菌株的细胞内 ATP 含量之间没有相关性，但 CC30 菌株的膜电位略低于非 CC30 组。CC30 菌株先前与慢性和复发性感染有关，我们假设通过 持久型测定显示的谱系特异性特征与观察到的疾病临床谱之间可能存在相关性。
