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

Abstract

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 Fcγ 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.