Escherichia coli is the most common Gram‐negative bacillary organism causing neonatal meningitis. Escherichia coli meningitis remains an important cause of mortality and morbidity, but the pathogenesis of E. coli penetration of the blood–brain barrier remains incompletely understood. Escherichia coli entry into the brain occurs in the meningeal and cortex capillaries, not in the choroid plexus, and exploits epidermal growth factor receptor (EGFR) and cysteinyl leukotrienes (CysLTs) for invasion of the blood–brain barrier. The present study examined whether EGFR and CysLTs are inter‐related in their contribution to E. coli invasion of the blood–brain barrier and whether counteracting EGFR and CysLTs is a beneficial adjunct to antibiotic therapy of E. coli meningitis. We showed that (a) meningitis isolates of E. coli exploit EGFR and CysLTs for invasion of the blood–brain barrier, (b) the contribution of EGFR is upstream of that of CysLTs, and (c) counteracting EGFR and CysLTs as an adjunctive therapy improved the outcome (survival, neuronal injury and memory impairment) of animals with E. coli meningitis. These findings suggest that investigation of host factors contributing to E. coli invasion of the blood–brain barrier will help in enhancing the pathogenesis and development of new therapeutic targets for E. coli meningitis in the era of increasing resistance to conventional antibiotics.

中文翻译：

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针对大肠杆菌对血脑屏障的入侵，以研究大肠杆菌脑膜炎的发病机制和治疗进展。

大肠杆菌是引起新生儿脑膜炎的最常见的革兰氏阴性菌。大肠杆菌脑膜炎仍然是死亡率和发病率的重要原因，但大肠杆菌穿透血脑屏障的发病机制仍未完全了解。大肠杆菌进入大脑发生在脑膜和皮质毛细血管中，而不是在脉络丛中，并利用表皮生长因子受体 (EGFR) 和半胱氨酰白三烯 (CysLT) 侵入血脑屏障。本研究检查了 EGFR 和 CysLTs 对大肠杆菌的贡献是否相互关联血脑屏障的侵入以及对抗 EGFR 和 CysLT 是否是大肠杆菌脑膜炎抗生素治疗的有益辅助手段。我们表明 (a)大肠杆菌的脑膜炎分离株利用 EGFR 和 CysLTs 入侵血脑屏障，(b) EGFR 的贡献在 CysLTs 的上游，以及 (c) 抵消 EGFR 和 CysLTs 作为辅助治疗改善了大肠杆菌脑膜炎动物的结果（存活、神经元损伤和记忆障碍）。这些发现表明，对导致大肠杆菌侵入血脑屏障的宿主因素的调查将有助于增强大肠杆菌的发病机制和新治疗靶点的开发 在对常规抗生素耐药性增加的时代，脑膜炎。