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

The extracellular pathogen enteropathogenic Escherichia coli (EPEC) uses a type III secretion system to inhibit its uptake by macrophages. We show tha t 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 phosphatidylinosit ol (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 wi ld type, suggesting that EPEC blocks a PI 3-kinase-dependent phagocytic pat hway. EPEC specifically inhibited Fc gamma receptor- but not CR3-receptor m ediated phagocytosis of opsonized zymosan, We showed that EPEC inhibits PI 3-kinase activity rather than its recruitment to the site of bacterial cont act. Phagocytosis of a secretion mutant correlated with the association of PI 3-kinase with tyrosine-phosphorylated proteins, which wild-type EPEC pre vented. These results show that EPEC blocks its uptake by inhibiting a PI 3 -kinase-mediated pathway, and translocates effecters other than Tir to inte rfere with actin-driven host cell processes. This constitutes a novel mecha nism of phagocytosis avoidance by an extracellular pathogen.