Environmental pressure-driven adaptive evolution mediated by clpC operon in Staphylococcus aureus

XIE Jinru; WANG Lei; WANG Xiukun; LI Congran; HOU Lei; YANG Xinyi; LIU Jianhua; LI Guoqing; YOU Xuefu

doi:10.13506/j.cnki.jpr.2025.06.001

Abstract：Objective To investigate the role of clpC operon in the adaptive evolution of Staphylococcus aureus.Meth-ods 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 upregu-lation 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 in-fection experiments indicated that SA2503 induced more severe pulmonary tissue damage,accompanied by significantly ele-vated serum levels of LDH,ALT,and CRP.Conclusion This study reveals a novel adaptive evolutionary pathway in clinicalS.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.