title: CEACAM1 recognition by bacterial pathogens is species-specific.
abstract: 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.
authors.affiliation: Lehrstuhl für Zellbiologie, Universität Konstanz, Mailbox X908, 78457 Konstanz, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Voges
authors.forename: Verena
authors.initials: V
authors.lastname: Bachmann
authors.forename: Robert
authors.initials: R
authors.lastname: Kammerer
authors.forename: Uri
authors.initials: U
authors.lastname: Gophna
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
mesh_terms: 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
chemical_list: D018829:Adhesins, Bacterial; D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules
references.citation: Gene. 2001 Feb 7;264(1):105-12
references.pmid: 11245984
references.citation: J Exp Med. 2004 Jan 5;199(1):35-46
references.pmid: 14707113
references.citation: J Exp Med. 2001 Feb 5;193(3):281-95
references.pmid: 11157049
references.citation: J Biol Chem. 1993 Jul 25;268(21):15510-6
references.pmid: 8101840
references.citation: Semin Cancer Biol. 1999 Apr;9(2):67-81
references.pmid: 10202129
references.citation: EMBO J. 2008 Jun 18;27(12):1779-89
references.pmid: 18497748
references.citation: J Virol. 1998 Sep;72(9):7237-44
references.pmid: 9696818
references.citation: J Virol. 1993 Jan;67(1):1-8
references.pmid: 8380065
references.citation: EMBO J. 2000 Nov 15;19(22):5989-99
references.pmid: 11080146
references.citation: J Virol. 1997 Feb;71(2):1688-91
references.pmid: 8995701
references.citation: J Microbiol Methods. 2006 May;65(2):301-10
references.pmid: 16185780
references.citation: Cell Microbiol. 2001 Jan;3(1):33-44
references.pmid: 11207618
references.citation: BMC Evol Biol. 2007 Oct 18;7:196
references.pmid: 17945019
references.citation: J Virol. 2004 Sep;78(18):10156-65
references.pmid: 15331748
references.citation: J Microbiol Methods. 2007 Mar;68(3):478-85
references.pmid: 17126432
references.citation: Microb Pathog. 1993 May;14(5):389-98
references.pmid: 8366816
references.citation: Cell Microbiol. 2008 May;10(5):1074-92
references.pmid: 18081725
references.citation: Infect Immun. 1991 Jun;59(6):2051-7
references.pmid: 1674739
references.citation: Science. 1975 Dec 12;190(4219):1103-5
references.pmid: 810892
references.citation: Infect Immun. 2002 Apr;70(4):1715-23
references.pmid: 11895933
references.citation: Mol Microbiol. 2001 Feb;39(4):850-62
references.pmid: 11251807
references.citation: Mol Microbiol. 2000 May;36(4):784-95
references.pmid: 10844667
references.citation: Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1716-20
references.pmid: 8383324
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17142-7
references.pmid: 16275906
references.citation: Infect Immun. 2008 Nov;76(11):5322-9
references.pmid: 18678656
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14851-6
references.pmid: 8962144
references.citation: BMC Biol. 2010 Feb 04;8:12
references.pmid: 20132533
references.citation: Mol Microbiol. 1996 Dec;22(5):941-50
references.pmid: 8971715
references.citation: Mol Microbiol. 2003 Apr;48(1):117-29
references.pmid: 12657049
references.citation: J Cell Biol. 2005 Aug 29;170(5):825-36
references.pmid: 16115956
references.citation: Trends Microbiol. 2001 Mar;9(3):119-25
references.pmid: 11239789
references.citation: Cell Microbiol. 2007 Feb;9(2):329-46
references.pmid: 16953805
references.citation: J Microbiol Methods. 2004 Oct;59(1):23-32
references.pmid: 15325750
references.citation: Nat Biotechnol. 2004 Apr;22(4):445-9
references.pmid: 14990965
references.citation: Genomics. 2005 Nov;86(5):566-80
references.pmid: 16139472
references.citation: Mol Microbiol. 1988 Nov;2(6):827-9
references.pmid: 2850444
references.citation: Gene. 2004 Sep 15;339:99-109
references.pmid: 15363850
references.citation: Tumour Biol. 2000 Mar-Apr;21(2):63-81
references.pmid: 10686536