CEACAM1 recognition by bacterial pathogens is species-specific.
BACKGROUND
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an immunoglobulin (Ig)-related glycoprotein, serves as cellular receptor for a variety of Gram-negative bacterial pathogens associated with the human mucosa. In particular, Neisseria gonorrhoeae, N. meningitidis, Moraxella catarrhalis, and Haemophilus influenzae possess well-characterized CEACAM1-binding adhesins. CEACAM1 is typically involved in cell-cell attachment, epithelial differentiation, neovascularisation and regulation of T-cell proliferation, and is one of the few CEACAM family members with homologues in different mammalian lineages. However, it is unknown whether bacterial adhesins of human pathogens can recognize CEACAM1 orthologues from other mammals.


RESULTS
Sequence comparisons of the amino-terminal Ig-variable-like domain of CEACAM1 reveal that the highest sequence divergence between human, murine, canine and bovine orthologues is found in the beta-strands comprising the bacteria-binding CC'FG-face of the Ig-fold. Using GFP-tagged, soluble amino-terminal domains of CEACAM1, we demonstrate that bacterial pathogens selectively associate with human, but not other mammalian CEACAM1 orthologues. Whereas full-length human CEACAM1 can mediate internalization of Neisseria gonorrhoeae in transfected cells, murine CEACAM1 fails to support bacterial internalization, demonstrating that the sequence divergence of CEACAM1 orthologues has functional consequences with regard to bacterial recognition and cellular invasion.


CONCLUSIONS
Our results establish the selective interaction of several human-restricted bacterial pathogens with human CEACAM1 and suggest that co-evolution of microbial adhesins with their corresponding receptors on mammalian cells contributes to the limited host range of these highly adapted infectious agents.
Voges
Maike
M
Lehrstuhl für Zellbiologie, Universität Konstanz, Mailbox X908, 78457 Konstanz, Germany.
Bachmann
Verena
V
Kammerer
Robert
R
Gophna
Uri
U
Hauck
Christof R
CR
D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D018829:Adhesins, Bacterial; D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules
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