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抗生素亚抑菌浓度对ATCC 27853群体感应和毒力因子的生长阶段依赖性调控

Growth-Phase-Dependent Modulation of Quorum Sensing and Virulence Factors in ATCC 27853 by Sub-MICs of Antibiotics.

作者信息

Amer Ahmed Noby, Attia Nancy, Baecker Daniel, Mansour Rasha Emad, El-Soudany Ingy

机构信息

Microbiology and Immunology Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria 21648, Egypt.

Microbiology Department, Medical Research Institute, Alexandria University, Alexandria 26571, Egypt.

出版信息

Antibiotics (Basel). 2025 Jul 21;14(7):731. doi: 10.3390/antibiotics14070731.

Abstract

: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. : The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minimum inhibitory concentration (sub-MIC) modulates the physiology of is examined in this study using growth-phase-resolved analysis. : Standard strain cultures were exposed to ¼ and ½ MIC to determine the growth kinetics under antibiotic stress. The study measured protease and pyocyanin production and the expression level of important quorum sensing and virulence genes (/, /, /, and ) at different growth phases. : Meropenem produced the most noticeable growth suppression at ½ MIC. Sub-MIC antibiotics did not completely stop growth, but caused distinct, dose-dependent changes. Azithromycin eliminated protease activity in all phases and had a biphasic effect on pyocyanin. Ciprofloxacin consistently inhibited both pyocyanin and protease in all phases. The effects of amikacin varied by phase and dose, while β-lactams markedly increased pyocyanin production during the log phase. In contrast to the plateau phase, when expression was often downregulated or unchanged, most quorum-sensing- and virulence-associated genes showed significant upregulation during the death phase under sub-MIC exposure. : These findings indicate that sub-MIC antibiotics act as biochemical signal modulators, preserving stress-adapted sub-populations that, in late growth phases, activate quorum sensing and stress tolerance pathways.

摘要

亚抑制浓度的抗生素可重塑细菌调控网络,影响其毒力。本研究采用生长阶段解析分析方法,探究低于最低抑菌浓度(亚MIC)的特定抗生素(环丙沙星、阿米卡星、阿奇霉素、头孢他啶和美罗培南)暴露对铜绿假单胞菌生理学的影响。将标准铜绿假单胞菌菌株培养物暴露于1/4和1/2 MIC浓度下,以确定抗生素应激下的生长动力学。该研究测量了不同生长阶段蛋白酶和绿脓菌素的产生以及重要群体感应和毒力基因(lasI、lasR、rhlI和rhlR)的表达水平。美罗培南在1/2 MIC时产生最显著的生长抑制。亚MIC抗生素并未完全停止生长,但导致了明显的剂量依赖性变化。阿奇霉素在所有阶段均消除了蛋白酶活性,并对绿脓菌素有双相作用。环丙沙星在所有阶段均持续抑制绿脓菌素和蛋白酶。阿米卡星的作用因阶段和剂量而异,而β-内酰胺类药物在对数期显著增加了绿脓菌素的产生。与稳定期表达常下调或不变相反,在亚MIC暴露下,大多数群体感应和毒力相关基因在死亡期显示出显著上调。这些发现表明,亚MIC抗生素作为生化信号调节剂,保留了适应应激的亚群,这些亚群在生长后期激活群体感应和应激耐受途径。

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