Torabian Panteha, Singh Navraj, Crawford James, Gonzalez Gabriela, Burgado Nicholas, Videva Martina, Miller Aidan, Perdue Janai, Dinu Milena, Pietropaoli Anthony, Gaborski Thomas, Michel Lea Vacca
Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, USA.
School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, NY, USA.
Int J Antimicrob Agents. 2025 Jan;65(1):107384. doi: 10.1016/j.ijantimicag.2024.107384. Epub 2024 Nov 13.
Sepsis, a leading cause of death in hospitals, can be defined as a dysregulated host inflammatory response to infection, which can lead to tissue damage, organ failure and cardiovascular complications. Although there is no cure for sepsis, the condition is typically managed with broad-spectrum antibiotics to eliminate any potential bacterial source of infection. However, a potential side effect of antibiotic treatment is the enhanced release of bacterial extracellular vesicles (BEVs), membrane-bound nanoparticles containing proteins and other biological molecules from their parent bacterium. Some of the Gram-negative extracellular vesicle (EV) cargo, including peptidoglycan associated lipoprotein and outer membrane protein A, have been shown to induce both acute and chronic inflammation in host tissue. It was hypothesized that the antibiotic concentration and mechanism of action may affect the amount of released BEVs, which could potentially exacerbate the host inflammatory response. This study evaluated nine clinically relevant antibiotics for their effect on EV release from Escherichia coli. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycoside antibiotics caused less vesiculation. Further study is warranted to corroborate the correlation between an antibiotic's mechanism of action and its effect on EV release, but these results underline the importance of antibiotic choice when treating patients with sepsis.
脓毒症是医院内主要的死亡原因之一，可定义为宿主对感染的炎症反应失调，这可能导致组织损伤、器官衰竭和心血管并发症。尽管脓毒症无法治愈，但通常使用广谱抗生素来治疗，以消除任何潜在的细菌感染源。然而，抗生素治疗的一个潜在副作用是细菌细胞外囊泡（BEV）的释放增加，BEV是一种膜结合纳米颗粒，含有来自其亲本细菌的蛋白质和其他生物分子。一些革兰氏阴性细胞外囊泡（EV）的成分，包括肽聚糖相关脂蛋白和外膜蛋白A，已被证明可在宿主组织中诱导急性和慢性炎症。据推测，抗生素的浓度和作用机制可能会影响释放的BEV数量，这可能会加剧宿主的炎症反应。本研究评估了九种临床相关抗生素对大肠杆菌释放EV的影响。几种β-内酰胺类抗生素导致的EV释放显著更多，而喹诺酮类和氨基糖苷类抗生素导致的囊泡形成较少。有必要进行进一步研究以证实抗生素的作用机制与其对EV释放的影响之间的相关性，但这些结果强调了在治疗脓毒症患者时选择抗生素的重要性。
