This study was designed to evaluate phenotypic and genotypic properties of persister cells formed by Staphylococcus aureus ATCC 15564 (SAWT), oxacillin-induced S. aureus (SAOXA), ciprofloxacin-induced S. aureus (SACIP), and clinically isolated multidrug-resistant S. aureus CCARM 3080 (SAMDR). The dose-dependent biphasic killing patterns were observed for SAWT, SAOXA, SACIP, and SAMDR in response to twofold minimum inhibitory concentrate (MIC) of ciprofloxacin. The surviving cells of SAWT, SAOXA, SACIP, and SAMDR after twofold MIC of ciprofloxacin treatment were analyzed using a metabolic-based assay to estimate the fractions of persister cells. The least persister formation was induced in SACIP after twofold MIC of ciprofloxacin treatment, showing 58% of persistence. The lowest fitness cost of resistance was observed for the recovered persister cells of SACIP (relative fitness = 0.95), followed by SAMDR (relative fitness = 0.70), while the highest fitness cost was observed for SAWT (relative fitness = 0.26). The mRNA transcripts were analyzed by RT-PCR assay in recovered persister cells pre-incubated with ciprofloxacin. The highest expression levels of stress-related genes (dnaK and groEL) and efflux pump-related genes (mepR, norA, and norB) were observed in the recovered persister cells of SAOXA and SAMDR. This study provides valuable information for understanding crosstalk between antibiotic resistance, tolerance, and persistence in different antibiotic-resistant S. aureus strains.

中文翻译：

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抗生素应激在表型向耐药性金黄色葡萄球菌持久性细胞转换中的作用

本研究旨在评估由金黄色葡萄球菌ATCC 15564（SAWT），奥沙西林诱导的金黄色葡萄球菌（SAOXA），环丙沙星诱导的金黄色葡萄球菌（SACIP）和临床分离的耐多药性S形成的持久性细胞的表型和基因型特性金黄色CCARM 3080（SAMDR）。观察到环丙沙星的最小抑菌浓度为两倍时，SAWT，SAOXA，SACIP和SAMDR的剂量依赖性双相杀伤模式。使用基于代谢的分析方法分析环丙沙星治疗的2倍MIC后SAWT，SAOXA，SACIP和SAMDR的存活细胞，以评估持久性细胞的分数。环丙沙星治疗的两倍MIC后，SACIP中诱导的持久性形成最少，显示持久性为58％。回收的SACIP持久性细胞的抗性适应性成本最低（相对适应性= 0.95），其次是SAMDR（相对适应性= 0.70），而SAWT的抗性适应性成本最高（相对适应性= 0.26）。通过RT-PCR分析在与环丙沙星预孵育的回收的持久性细胞中分析mRNA转录物。在回收的SAOXA和SAMDR持久性细胞中观察到应激相关基因（dnaK和groEL）和外排泵相关基因（mepR，norA和norB）的最高表达水平。这项研究为理解抗生素耐药性，耐受性和不同抗生素耐药性金黄色葡萄球菌菌株的持久性之间的串扰提供了有价值的信息。而SAWT的健身成本最高（相对健身= 0.26）。通过RT-PCR分析在与环丙沙星预孵育的回收的持久性细胞中分析mRNA转录物。在回收的SAOXA和SAMDR持久性细胞中观察到应激相关基因（dnaK和groEL）和外排泵相关基因（mepR，norA和norB）的最高表达水平。这项研究为理解抗生素耐药性，耐受性和不同抗生素耐药性金黄色葡萄球菌菌株的持久性之间的串扰提供了有价值的信息。而SAWT的健身成本最高（相对健身= 0.26）。通过RT-PCR分析在与环丙沙星预孵育的回收的持久性细胞中分析mRNA转录物。在回收的SAOXA和SAMDR持久性细胞中观察到应激相关基因（dnaK和groEL）和外排泵相关基因（mepR，norA和norB）的最高表达水平。这项研究为理解抗生素耐药性，耐受性和不同抗生素耐药性金黄色葡萄球菌菌株的持久性之间的串扰提供了有价值的信息。和norB）在回收的SAOXA和SAMDR的持久性细胞中观察到。这项研究为理解抗生素耐药性，耐受性和不同抗生素耐药性金黄色葡萄球菌菌株的持久性之间的串扰提供了有价值的信息。和norB）在回收的SAOXA和SAMDR的持久性细胞中观察到。这项研究为理解抗生素耐药性，耐受性和不同抗生素耐药性金黄色葡萄球菌菌株的持久性之间的串扰提供了有价值的信息。