Binding of intimin with Tir on the bacterial surface is prerequisite for the barrier disruption induced by enteropathogenic Escherichia coli.
Enteropathogenic Escherichia coli (EPEC) infects intestinal epithelial cells and perturbs the intestinal barrier that limits the paracellular movement of molecules. The disruption of the barrier is mediated by the effectors translocated into the host cells through the bacterial type III secretion system (TTSS). A previous report has described the importance of a bacterial outer membrane protein, intimin, in EPEC-mediated disruption of the barrier, and proposed that intimin, in concert with a host intimin receptor, controls the activity of the translocated barrier-disrupting effectors [P. Dean, B. Kenny, Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein, Mol. Microbiol. 54 (2004) 665-675]. In this study, we found that the importance of intimin is in its ability to bind a bacterial intimin receptor, Tir. Additionally, the impaired ability of an intimin-negative mutant was not restored by co-infection with intimin-expressing TTSS mutants. Collectively, the results in this study favor an alternative scenario explaining the importance of intimin, that the binding of intimin with Tir on the bacterial surface triggers or promotes the translocation of factors required for the efficient disruption of the barrier. Thus, the interaction of intimin with Tir may serve as a molecular switch that controls the delivery of virulence factors into the host cells.
Miyake
Masami
M
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-City, Osaka 565-0871, Japan. mami@biken.osaka-u.ac.jp
Hanajima
Miyuki
M
Matsuzawa
Takeshi
T
Kobayashi
Chiho
C
Minami
Masayoshi
M
Abe
Akio
A
Horiguchi
Yasuhiko
Y
D018829:Adhesins, Bacterial / Q000378:metabolism*; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D004926:Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D011485:Protein Binding; D011504:Protein-Losing Enteropathies / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*
D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; C073819:eaeA protein, E coli