Subanovic Monika, Frawley Dean, Tierney Ciara, Velasco-Torrijos Trinidad, Walsh Fiona
Department of Biology, The Kathleen Lonsdale Human Health Institute, Maynooth University, Maynooth, Ireland.
Department of Chemistry, The Kathleen Lonsdale Human Health Institute, Maynooth University, Maynooth, Ireland.
NPJ Antimicrob Resist. 2025 Sep 16;3(1):80. doi: 10.1038/s44259-025-00147-7.
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.
本研究采用全面的蛋白质组学和代谢组学分析，以表征优先病原体——大肠杆菌、肺炎克雷伯菌、粪肠球菌和金黄色葡萄球菌——在亚抑制浓度抗生素作用下的适应性细胞机制。尽管代谢组学发生了显著扰动，但一些病原体的蛋白质组变化极小或无显著变化。值得注意的是，三甲胺代谢在所有物种中均持续改变，表明其在抗生素应激下的生存中发挥作用。金黄色葡萄球菌和粪肠球菌对氯霉素的共同适应性反应与翻译、氧化应激管理、蛋白质折叠和稳定性、生物膜形成能力、甘氨酸代谢和渗透保护有关。季胺和三甲胺代谢的改变表明，在抗生素应激下存在替代的氮和碳利用途径。在金黄色葡萄球菌中，万古霉素抑制代谢，包括D-丙氨酸代谢以及全局调节因子LytR、CodY和CcpA。这些发现为早期抗菌耐药机制提供了见解，并突出了与抗生素耐受性相关的关键蛋白质和代谢物。
