Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells

Abstract

Adhesion to epithelial cells1 and flagella-mediated motility are critical virulence traits for many Gram-negative pathogens, including enterotoxigenic Escherichia coli (ETEC)2, a major cause of diarrhoea in travellers and children in developing countries3,4. Many flagellated pathogens export putative adhesins belonging to the two-partner secretion (TPS) family5. However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic Escherichia coli6, mimics and interacts with highly conserved regions of flagellin, the major subunit of flagella, and that these interactions are critical for adherence and intestinal colonization. Although conserved regions of flagellin are mostly buried in the flagellar shaft7, our results suggest that they are at least transiently exposed at the tips of flagella where they capture EtpA adhesin molecules for presentation to eukaryotic receptors. Similarity of EtpA to molecules encoded by other motile pathogens suggests a potential common paradigm for bacterial adhesion, while participation of conserved regions of flagellin in adherence has implications for development of vaccines for Gram-negative pathogens.

Mecanismos de virulencia de Escherichia coli enteropatógena

“…Para la adherencia de ECET a las células epiteliales, la bacteria expresa la EtpA, exoproteína de adhesión (TPS: two-partner secretion) situada al extremo del flagelo, para permitir que los CFs se adhieran a éstas. Inmediatamente después, el auto-transportador EatA (EatA: autotransporter A) incluida en el grupo de las serin-proteasas (SPATEs: serine protease autotransporter of Enterobacteriaceae) inhiben la actividad de EtpA, lo que da origen a la adhesión de ECET a los enterocitos por el loci toxigénico de invasión A (Tia: toxigenic invasion loci A), una proteína de membrana externa y el loci toxigénico de invasión B (TibA: toxigenic invasion loci B) (Figura 3) [69][70][71][72] . P) 50,51 , que contribuye a la formación de microcolonias y a la adhesión a células epiteliales de colon T84 51 (Figura 2b); b) Transcitosis: mediante vesículas la toxina pasa de un espacio extracelular a otro (Figura 2b) 52 .…”

Infection strategies of enteric pathogenic Escherichia coli

“…35 While ETEC binds to leaf surfaces through the flagellum shaft, 36 a novel adhesin, EtpA, located on the tip of ETEC flagella mediates attachment to mammalian host cells. 37 EtpA is degraded by the serine protease autotransporter of Enterobacteriaceae (SPATE), EatA, thereby modulating bacterial adhesion and accelerating delivery of heat labile (LT) toxin into host cells. 38 A model of sequential attachment is proposed whereby the long-range flagella-EtpA first anchors the bacterium to the host cell and allows shorter CFs to interact.…”

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

“…ETEC strains may possesses one or more nonfimbrial adhesins (recently reviewed by Fleckenstein et al [104]). One of these, EtpA, is a glycoprotein that links flagella to host cells and may be a potential vaccine candidate [105,106].…”