Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Department of Biological Sciences, Faculty of Science and Technology, Sunway University, Selangor, Malaysia.
Traffic. 2017 Nov;18(11):733-746. doi: 10.1111/tra.12508. Epub 2017 Sep 20.
Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.
真核细胞利用多种内吞途径来特异性摄取配体或分子，而这些途径通常被病原体劫持以实现宿主细胞入侵。大肠杆菌 K1 是一种引起新生儿脑膜炎的致病菌，它可入侵血脑屏障的内皮细胞，但进入途径尚不清楚。在这里，我们证明细菌会触发肌动蛋白介导的摄取途径，刺激液相反响、细胞膜隆起和巨胞饮作用。摄取途径需要完整的脂筏，如胆固醇耗竭所示。通过使用各种扰动剂，我们证明小 Rho GTPases 及其下游效应物对细菌入侵有显著影响。此外，网格蛋白介导的内吞作用似乎在大肠杆菌 K1 的摄取中起着间接作用。数据表明，细菌在 Rho GTPases 之间产生复杂的相互作用，以增加它们通过巨胞饮作用进入人脑微血管内皮细胞的机会。
