【摘要】 目的 探讨clpC操纵子在金黄色葡萄球菌(Staphylococcus aureus)适应性进化中的作用。方法 从一位菌血症患者体内分离到两株金黄色葡萄球菌(SA2503和SA3001),进行全基因组测序、基因表达分析、体外表型测定、小鼠血流感染研究，比较两株菌株的基因组差异、应激反应、毒力以及体内感染情况，评估菌株生物学特性。结果 基因组分析显示SA2503菌株基因组中存在一个2 400 bp的插入突变，拷贝自clpC操纵子的部分序列，导致了热休克蛋白调节网络重塑，clpC、mcsA、mcsB和ctsR基因表达上调。SA2503在标准培养条件下生长能力略低于SA3001,但在氧化应激条件下生长能力更强。小鼠血流感染实验表明，SA2503对肺组织的损伤更为严重，血清LDH、ALT、CRP水平明显升高。结论 该研究揭示了临床中金黄色葡萄球菌新的适应性进化路径，即通过clpC操纵子部分片段的插入突变引起抗氧化应激能力和毒力增强，使菌株在强氧化应激环境中具有生存优势，但随着氧化应激环境的改变，此优势会成为劣势，促进菌株的动态演变。此发现为理解金黄色葡萄球菌在临床环境中的适应性进化机制提供了新见解。更多还原

【Abstract】 Objective To investigate the role of clpC operon in the adaptive evolution of Staphylococcus aureus.Methods Two S.aureus strains(SA2503 and SA3001) were isolated from a patient with bacteremia.Whole genome sequencing, gene expression analysis, in vitro phenotypic characterization, and mouse bloodstream infection studies were conducted to compare genomic differences, stress responses, virulence, and in vivo infection patterns between the two strains, evaluating their biological characteristics.Results Genomic analysis revealed a 2 400 bp insertion mutation in the genome of SA2503,which is copied from part of the clpC operon, leading to remodeling of the heat shock protein regulatory network and upregulation of clpC,mcsA,mcsB,and ctsR genes.While SA2503 exhibited slightly reduced growth capacity compared to SA3001 under standard culture conditions, it demonstrated significantly stronger growth under oxidative stress.Mouse bloodstream infection experiments indicated that SA2503 induced more severe pulmonary tissue damage, accompanied by significantly elevated serum levels of LDH,ALT,and CRP.Conclusion This study reveals a novel adaptive evolutionary pathway in clinical S.aureus,mediated by insertional mutagenesis of partial clpC operon that simultaneously enhances oxidative stress resistance and virulence, giving the strain a survival advantage in high oxidative stress environment.However, as the oxidative stress environment changes, this advantage becomes a disadvantage, promoting dynamic evolution of the strain.This finding provides new insights into the mechanisms of adaptive evolution of Staphylococcus aureus in clinical environments.更多还原