Li Ying, Zhang Luhua, Zhou Yingshun, Zhang Zhikun, Zhang Xinzhuo
Department of Immunology, College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, PR China.
Department of Pathogenic Biology, College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, PR China.
J Med Microbiol. 2018 Mar;67(3):273-281. doi: 10.1099/jmm.0.000680. Epub 2018 Jan 19.
Persister cells, a subpopulation of tolerant cells within the bacterial culture, are commonly thought to be responsible for antibiotic therapy failure and infection recurrence. Klebsiella pneumoniae is a notorious human pathogen for its increasing resistance to antibiotics and wide involvement in severe infections. In this study, we aimed to investigate the persister subpopulation of K. pneumoniae.
The presence of persisters in K. pneumoniae was determined by treatment with high concentrations of antibiotics, used alone or in combination. The effect of low level of antibiotics on persister formation was investigated by pre-exposure of cells to antibiotics with low concentrations followed by higher doses. The dependence of persister levels on growth phase was determined by measuring the survival ability of cells along the growth stages upon exposure to a high concentration of antibiotic. Analysis on persister type was carried out by persister elimination assays.Results/Key findings. We show that K. pneumoniae produces high levels of tolerant persister cells to survive treatment by a variety of high concentrations of bactericidal antibiotics and persister formation is prevalent among K. pneumoniae clinical strains. Besides, we find that persister cells can be induced by low concentrations of antibiotics. Finally, we provide evidence that persister formation is growth phase-dependent and Type II persisters dominate the persister subpopulation during the entire exponential phase of K. pneumoniae.
Our study describes the formation of tolerant persister cells that allow survival of treatment by high concentrations of antibiotics in K. pneumoniae.
持留菌细胞是细菌培养物中耐受细胞的一个亚群，通常被认为是抗生素治疗失败和感染复发的原因。肺炎克雷伯菌是一种臭名昭著的人类病原体，因其对抗生素的耐药性不断增加且广泛参与严重感染。在本研究中，我们旨在调查肺炎克雷伯菌的持留菌亚群。
通过单独或联合使用高浓度抗生素处理来确定肺炎克雷伯菌中持留菌的存在。通过将细胞预先暴露于低浓度抗生素后再给予更高剂量来研究低水平抗生素对持留菌形成的影响。通过测量细胞在暴露于高浓度抗生素后的生长阶段的存活能力来确定持留菌水平对生长阶段的依赖性。通过持留菌消除试验对持留菌类型进行分析。结果/主要发现。我们表明，肺炎克雷伯菌产生高水平的耐受持留菌细胞，以在多种高浓度杀菌抗生素的处理下存活，并且持留菌形成在肺炎克雷伯菌临床菌株中普遍存在。此外，我们发现低浓度抗生素可诱导持留菌细胞。最后，我们提供证据表明持留菌的形成依赖于生长阶段，并且在肺炎克雷伯菌的整个指数生长期，II型持留菌在持留菌亚群中占主导地位。
我们的研究描述了耐受持留菌细胞的形成，这些细胞使得肺炎克雷伯菌能够在高浓度抗生素的处理下存活。
