title: Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa.
abstract: Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa.
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Muenzner
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Kengmo Tchoupa
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Klauser
authors.affiliation: Lehrstuhl Biochemische Pharmakologie, Fachbereich Biologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunner
authors.affiliation: Institut für Hygiene, Universität Münster, Münster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Putze
authors.affiliation: Institut für Hygiene, Universität Münster, Münster, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dobrindt
authors.affiliation: Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, Konstanz, Germany.|Konstanz Research School Chemical Biology, Universität Konstanz, Konstanz, Germany.
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D015153:Blotting, Western; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009092:Mucous Membrane / Q000378:metabolism / Q000382:microbiology*; D014566:Urogenital System / Q000378:metabolism / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*
chemical_list: D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules