title: Outer membrane protein P1 is the CEACAM-binding adhesin of Haemophilus influenzae.
abstract: Haemophilus influenzae is a Gram-negative pathogen colonizing the upper respiratory tract mucosa. H. influenzae is one of several human-restricted bacteria, which bind to carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on the epithelium leading to bacterial uptake by the eukaryotic cells. Adhesion to CEACAMs is thought to be mediated by the H. influenzae outer membrane protein (OMP) P5. However, CEACAMs still bound to H. influenzae lacking OMP P5 expression, and soluble CEACAM receptor ectodomains failed to bind to OMP P5, when heterologously expressed in Escherichia coli. Screening of a panel of H. influenzae OMP mutants revealed that lack of OMP P1 completely abrogated CEACAM binding and supressed CEACAM-mediated engulfment of H. influenzae by epithelial cells. Moreover, ectopic expression of OMP P1 in E. coli was sufficient to induce CEACAM binding and to promote attachment to and internalization into CEACAM-expressing cells. Interestingly, OMP P1 selectively recognizes human CEACAMs, but not homologs from other mammals and this binding preference is preserved upon expression in E. coli. Together, our data identify OMP P1 as the bona fide CEACAM-binding invasin of H. influenzae. This is the first report providing evidence for an involvement of the major OMP P1 of H. influenzae in pathogenesis.
authors.affiliation: Lehrstuhl für Zellbiologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Arnaud Kengmo
authors.initials: AK
authors.lastname: Tchoupa
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lichtenegger
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Joachim
authors.initials: J
authors.lastname: Reidl
authors.affiliation: Lehrstuhl für Zellbiologie, 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: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001422:Bacterial Adhesion / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D057809:HEK293 Cells; D006193:Haemophilus influenzae / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; C067559:outer membrane protein P1, Haemophilus influenzae type b; C082912:outer membrane protein P5, Haemophilus