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

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. Several clathrin‐independent endocytic pathway components have been implicated as regulatory factors exploited by neonatal meningitis‐causing Escherichia coli K1 bacteria to infect host cells. Here, we demonstrate that the bacteria induce general cell ruffling, increased fluid phase uptake, and actin‐, Rho GTPase‐ and cholesterol‐dependent invasion, which all point to a requirement for macropinocytosis as the route of uptake by the bacteria into non‐phago...
Source: Traffic - Category: Research Authors: Tags: ORIGINAL ARTICLE Source Type: research