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Here, we demonstrate that the bacteria trigger an actin\u2010mediated 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 <jats:styled-content style=\"fixed-case\">GTPases<\/jats:styled-content> and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin\u2010mediated endocytosis appears to play an indirect role in <jats:italic>E. coli<\/jats:italic> <jats:styled-content style=\"fixed-case\">K1<\/jats:styled-content> uptake. The data suggest that the bacteria effect a complex interplay between the Rho <jats:styled-content style=\"fixed-case\">GTPases<\/jats:styled-content> to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tra12508-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1111\/tra.12508","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T06:27:46Z","timestamp":1502432866000},"page":"733-746","source":"Crossref","is-referenced-by-count":27,"title":["<i>Escherichia coli<\/i> K1 utilizes host macropinocytic pathways for invasion of brain microvascular endothelial cells"],"prefix":"10.1111","volume":"18","author":[{"given":"Lip Nam","family":"Loh","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M. 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