Systematic Deletion of Type III Secretion System Effectors in Enteropathogenic E. coli Unveils the Role of Non-LEE Effectors in A/E Lesion Formation

Abstract

Enteropathogenic E. coli (EPEC) is a diarrheagenic human pathogen. The hallmark of EPEC infection is the formation of the attaching and effacing (A/E) lesion in the intestinal epithelial cells, characterized by the effacement of brush border microvilli and the intimate bacterial attachment to the enterocyte in actinrich pedestal-like structures. The locus of enterocyte effacement (LEE) in the EPEC genome encodes a type III protein secretion system (T3SS) that translocates multiple effector proteins into the host cell to subvert cellular functions for the benefit of the pathogen. These effectors are encoded both within and outside the LEE. In vitro cell culture infections have shown that LEE effectors are required for intimate bacterial attachment to the epithelial cells, whereas non-LEE effectors mostly play a role in modulating inflammation and cell apoptosis in the gut epithelium. We constructed a set of EPEC mutant strains harboring deletions in the complete repertoire of genes encoding T3SS effectors. Infection of human intestinal in vitro organ cultures (IVOC) with these mutant strains surprisingly revealed that non-LEE effectors are also needed to induce efficient A/E lesion formation in the intestinal mucosal tissue.

A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3

“…We have previously shown that the primary virulence factor of EHEC, Shiga toxin, suppresses noncanonical inflammasome responses 20 . Similarly, T3SS effectors such as Tir and non-LEE encoded effector (Nle) proteins of EHEC inhibit TLR4-dependent NFκB-and MAPK-responses [57][58][59][60][61][62][63][64] .…”