A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation.

Enteropathogenic E. coli (EPEC) belongs to a group of bacterial pathogens that induce actin accumulation beneath adherent bacteria. We found that EPEC adherence to epithelial cells mediates the formation of fingerlike pseudopods (up to 10 microm) beneath bacteria. These actin‐rich structures also contain tyrosine phosphorylated host proteins concentrated at the pseudopod tip beneath adherent EPEC. Intimate bacterial adherence (and pseudopod formation) occurred only after prior bacterial induction of tyrosine phosphorylation of an epithelial membrane protein, Hp90, which then associates directly with an EPEC adhesin, intimin. These interactions lead to cytoskeletal nucleation and pseudopod formation. This is the first example of a bacterial pathogen that triggers signals in epithelial cells which activates receptor binding activity to a specific bacterial ligand and subsequent cytoskeletal rearrangement.

[1]  B. Finlay,et al.  Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. , 1991, Journal of cell science.

[2]  B. Finlay,et al.  Cytoskeletal composition of attaching and effacing lesions associated with enteropathogenic Escherichia coli adherence to HeLa cells , 1992, Infection and immunity.

[3]  M. Levine,et al.  Enteropathogenic Escherichia coli of classic serotypes associated with infant diarrhea: epidemiology and pathogenesis. , 1984, Epidemiologic reviews.

[4]  P. Sherman,et al.  Signal transduction in human epithelial cells infected with attaching and effacing Escherichia coli in vitro. , 1994, Gastroenterology.

[5]  S. Falkow,et al.  Genetic organization of the afimbrial adhesin operon and nucleotide sequence from a uropathogenic Escherichia coli gene encoding an afimbrial adhesin , 1985, Journal of bacteriology.

[6]  P. Williams,et al.  Actin accumulation at sites of bacterial adhesion to tissue culture cells: basis of a new diagnostic test for enteropathogenic and enterohemorrhagic Escherichia coli , 1989, Infection and immunity.

[7]  J. Yu,et al.  A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[8]  K. Magnusson,et al.  Target cell contact triggers expression and polarized transfer of Yersinia YopE cytotoxin into mammalian cells. , 1994, The EMBO journal.

[9]  C. Kocks,et al.  The actin‐based motility of the facultative intracellular pathogen Listeria monocytogenes , 1994, Molecular microbiology.

[10]  J. Kvittingen [Enteropathogenic Escherichia coli]. , 1966, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[11]  B. Finlay,et al.  Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake , 1992 .

[12]  G. Schoolnik,et al.  Characterization of fimbriae produced by enteropathogenic Escherichia coli , 1993, Journal of bacteriology.

[13]  B. Finlay,et al.  A diarrheal pathogen, enteropathogenic Escherichia coli (EPEC), triggers a flux of inositol phosphates in infected epithelial cells , 1994, The Journal of experimental medicine.

[14]  J. Yu,et al.  A second chromosomal gene necessary for intimate attachment of enteropathogenic Escherichia coli to epithelial cells , 1993, Journal of bacteriology.

[15]  G. Schoolnik,et al.  Sequence, localization and function of the invasin protein of Yersinia enterocoiitica , 1990, Molecular microbiology.

[16]  J. Nataro,et al.  A plasmid‐encoded type IV fimbrial gene of enteropathogenic Escherichia coli associated with localized adherence , 1992, Molecular microbiology.

[17]  J. R. Andrade,et al.  An endocytic process in HEp-2 cells induced by enteropathogenic Escherichia coli. , 1989, Journal of medical microbiology.

[18]  B. Finlay,et al.  Protein secretion by enteropathogenic Escherichia coli is essential for transducing signals to epithelial cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Patterning of the membrane cytoskeleton by the extracellular matrix. , 1990, Seminars in cell biology.

[20]  B. Finlay,et al.  Methods to study bacterial invasion , 1993 .

[21]  T. McDaniel,et al.  Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Williams,et al.  Intestinal epithelial cell protein phosphorylation in enteropathogenic Escherichia coli diarrhoea , 1992, The Lancet.

[23]  B. Finlay,et al.  Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake. , 1992, The EMBO journal.

[24]  G. Keusch,et al.  Construction and analysis of TnphoA mutants of enteropathogenic Escherichia coli unable to invade HEp-2 cells , 1990, Infection and immunity.

[25]  B. Finlay,et al.  The eaeB gene of enteropathogenic Escherichia coli is necessary for signal transduction in epithelial cells , 1994, Infection and immunity.

[26]  M. Levine,et al.  Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection. , 1993, The Journal of clinical investigation.

[27]  G. Dougan,et al.  Characterization of the C-terminal domains of intimin-like proteins of enteropathogenic and enterohemorrhagic Escherichia coli, Citrobacter freundii, and Hafnia alvei , 1994, Infection and immunity.

[28]  G. Keusch,et al.  A comparison of HEp-2 cell invasion by enteropathogenic and enteroinvasive Escherichia coli. , 1990, FEMS microbiology letters.

[29]  S. Falkow,et al.  Identification of invasin: A protein that allows enteric bacteria to penetrate cultured mammalian cells , 1987, Cell.

[30]  G. Cornelis,et al.  Translocation of a hybrid YopE‐adenylate cyclase from Yersinia enterocolitica into HeLa cells , 1994, Molecular microbiology.

[31]  J. Kaper,et al.  Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector , 1991, Infection and immunity.