PDF(Pubmed)
Abstract：
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). BEVs are membrane-bound nanoparticles produced by a variety of mechanisms, one of which includes the pinching-off of the outer membrane (in Gram-negative bacteria) to enclose proteins and other biological molecules for transport and intercellular communication. Some of the Gram-negative EV cargo, including Peptidoglycan associated lipoprotein (Pal) and Outer membrane protein A (OmpA), have been shown to induce both acute and chronic inflammation in host tissue. We hypothesize that antibiotic concentration and its mechanism of action can have an effect on the amount of released BEVs, which could potentially exacerbate the host inflammatory response. In this study, we evaluated nine clinically relevant antibiotics for their effect on EV release from Escherichia coli. EVs were characterized using immunoblotting, nanoparticle tracking analysis, and transmission electron microscopy. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycosides caused relatively 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 sepsis patients.
摘要：
脓毒症,医院死亡的主要原因，可以定义为宿主对感染的炎症反应失调，会导致组织损伤，器官衰竭,和心血管并发症。虽然没有治疗败血症的方法,这种情况通常使用广谱抗生素治疗，以消除任何潜在的细菌感染源。然而,抗生素治疗的潜在副作用是细菌胞外囊泡(BEV)的释放增强.BEV是通过多种机制产生的膜结合纳米颗粒，其中之一包括夹断外膜（在革兰氏阴性细菌中）以封闭蛋白质和其他生物分子以进行运输和细胞间通讯。一些革兰氏阴性电动汽车货物，包括肽聚糖相关的脂蛋白（帕尔）和外膜蛋白A（OmpA），已被证明在宿主组织中诱导急性和慢性炎症。我们假设抗生素浓度及其作用机制可以对释放的BEV的量产生影响，这可能会加剧宿主的炎症反应。在这项研究中,我们评估了9种临床相关抗生素对大肠杆菌EV释放的影响.电动汽车使用免疫印迹进行表征，纳米粒子跟踪分析，和透射电子显微镜。几种β-内酰胺抗生素导致了更多的EV释放，而喹诺酮和氨基糖苷类引起的囊泡相对较少。有必要进一步研究以证实抗生素的作用机制及其对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.
