Escherichia coli K1 utilises host macropinocytic pathways for invasion of brain microvascular endothelial cells.


Loh, LN; McCarthy, EMC; Narang, P; Khan, NA; Ward, TH; (2017) Escherichia coli K1 utilises host macropinocytic pathways for invasion of brain microvascular endothelial cells. Traffic (Copenhagen, Denmark). ISSN 1398-9219 DOI: 10.1111/tra.12508

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Abstract

Eukaryotic cells utilise 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 HBMEC.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
PubMed ID: 28799243
URI: http://researchonline.lshtm.ac.uk/id/eprint/4224329

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