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<p>This study employed a comprehensive proteomic and metabolomic analysis to characterize adaptive cellular mechanisms of priority pathogens—<i>Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium</i>, and <i>Staphylococcus aureus</i>—under sub-inhibitory concentrations of antibiotics. Despite significant metabolomic perturbations, some pathogens had minimal or no significant changes in their proteome. Notably, trimethylamine metabolism was consistently altered across all species, suggesting its role in survival under antibiotic stress. Shared adaptive responses to chloramphenicol in <i>S. aureus</i> and <i>E. faecium</i> are related to translation, oxidative stress management, protein folding and stability, biofilm formation capacity, glycine metabolism and osmoprotection. Alterations in quaternary amines and trimethylamine metabolism suggest alternative nitrogen and carbon utilization pathways in response to antibiotic stress. In <i>S. aureus</i>, vancomycin suppressed metabolism, including D-alanine metabolism, and global regulators LytR, CodY and CcpA. These findings offer insights into early antimicrobial resistance mechanisms and highlight critical proteins and metabolites linked to antibiotic tolerance.</p>

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Proteomic and metabolomic responses of priority bacterial pathogens to subinhibitory concentration of antibiotics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月16日

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  • Monika Subanovic,
  • Dean Frawley,
  • Ciara Tierney,
  • Trinidad Velasco-Torrijos,
  • Fiona Walsh

摘要

This study employed a comprehensive proteomic and metabolomic analysis to characterize adaptive cellular mechanisms of priority pathogens—Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, and Staphylococcus aureus—under sub-inhibitory concentrations of antibiotics. Despite significant metabolomic perturbations, some pathogens had minimal or no significant changes in their proteome. Notably, trimethylamine metabolism was consistently altered across all species, suggesting its role in survival under antibiotic stress. Shared adaptive responses to chloramphenicol in S. aureus and E. faecium are related to translation, oxidative stress management, protein folding and stability, biofilm formation capacity, glycine metabolism and osmoprotection. Alterations in quaternary amines and trimethylamine metabolism suggest alternative nitrogen and carbon utilization pathways in response to antibiotic stress. In S. aureus, vancomycin suppressed metabolism, including D-alanine metabolism, and global regulators LytR, CodY and CcpA. These findings offer insights into early antimicrobial resistance mechanisms and highlight critical proteins and metabolites linked to antibiotic tolerance.