贝塔乳酸抗生素通过ROS介导的脂质代谢重编程促进黄金葡萄球菌的细胞外囊生产

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Xiaonan Huang¹, Zhen Hu¹, Weilong Shang¹

¹Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing, Army Medical University, Chongqing, China.

Journal of extracellular vesicles

|May 2, 2025

概括

低于最低水平的β-乳糖胺抑制度显著增加了黄金菌菌中细菌细胞外囊泡 (EV) 的产生. 这种EV产量的增加是由活性氧物种和改变的脂质代谢介导的,为生物产品开发提供了新的策略.

科学领域:

微生物学微生物学
生物技术是生物技术.
药物发现药物发现药物发现

背景情况:

细菌细胞外囊泡 (EVs) 对生物制品如疫苗和药物输送有价值.
细菌的低自然EV产量限制了它们的广泛应用.
黄金葡萄球菌EV具有治疗和诊断用途的潜力.

研究的目的:

研究增强细菌EV生产的方法.
为了阐明低于最低抑制度 (MIC) 的β-乳酸盐增加Staphylococcus aureus中EV产量的机制.
在免疫学背景下评估改造EV的潜力.

主要方法:

用MIC以下β-乳糖抗生素治疗金黄色葡萄球菌菌株.
对青素结合蛋白 (PBP) 基因表达的分析.
对反应性氧物种 (ROS) 生产的评估.
转录学和脂质学分析.
在小鼠中评估EV载荷蛋白和免疫性.

主要成果:

亚MICβ-乳酸盐,特别是西林 (OXA),显著提高了S. aureus.中的EV产量.
β-乳糖治疗增加了PBP基因表达和ROS水平,PBP的失活促进了EV分泌.
由OXA诱导的ROS触发了脂质代谢重编程,包括增加的脂质过氧化,酸和酸生物合成,有助于EV生成.
来自OXA治疗细菌的EV显示出改变的蛋白质载荷,并在小鼠中增强了登革热EDIII特异性抗体诱导.

结论:

亚MICβ-乳酸通过涉及脂质代谢的ROS依赖途径有效增强细菌EV生产.
准PBP和调节ROS水平是增加细菌EV产量的可行策略.
修改后的细菌EV显示出提高免疫性潜力,支持其用于疫苗和其他生物制品的开发.

关键词:

黄金葡萄球菌黄金葡萄球菌细胞外囊泡细胞外囊泡脂质新陈代谢脂质新陈代谢青素结合蛋白质的青素结合蛋白质.有活性氧物种的反应性氧物种.这是β-lactam抗生素的抗生素.

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