Enteropathogenic Escherichia coli mediates antiphagocytosis through the inhibition of PI 3-kinase-dependent pathways

Celli, Jean; Olivier, Martin; Finlay, B. Brett
March 2001
EMBO Journal;3/15/2001, Vol. 20 Issue 6, p1245
Academic Journal
The extracellular pathogen enteropathogenic Escherichia coli (EPEC) uses a type III secretion system to inhibit its uptake by macrophages. We show that EPEC antiphagocytosis is independent of the translocated intimin receptor Tir and occurs by preventing F-actin polymerization required for bacterial uptake. EPEC-macrophage contact triggered activation of phosphatidylinositol (PI) 3-kinase, which was subsequently inhibited in a type III secretion-dependent manner. Inhibition of PI 3-kinase significantly reduced uptake of a secretion-deficient mutant, without affecting antiphagocytosis by the wild type, suggesting that EPEC blocks a PI 3-kinase-dependent phagocytic pathway. EPEC specifically inhibited Fc? receptor- but not CR3-receptor mediated phagocytosis of opsonized zymosan. We showed that EPEC inhibits PI 3-kinase activity rather than its recruitment to the site of bacterial contact. Phago cytosis of a secretion mutant correlated with the association of PI 3-kinase with tyrosine-phosphorylated proteins, which wild-type EPEC prevented. These results show that EPEC blocks its uptake by inhibiting a PI 3-kinase-mediated pathway, and translocates effectors other than Tir to interfere with actin-driven host cell processes. This constitutes a novel mechanism of phagocytosis avoidance by an extracellular pathogen.


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