title: Neisseria meningitidis has two independent modes of recognizing its human receptor CEACAM1.
abstract: BACKGROUND
  Several human-restricted gram-negative bacteria exploit carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for host colonization. For example, Neisseria meningitidis engages these human receptors via outer membrane proteins of the colony opacity-associated (Opa) protein family triggering internalization into non-phagocytic cells.
  
  
  RESULTS
  We report that a non-opaque strain of N. meningitidis selectively interacts with CEACAM1, but not other CEACAM family members. Using functional assays of bacterial adhesion and internalisation, microscopic analysis, and a panel of CEACAM1 deletion mutants we demonstrate that the engagement of CEACAM1 by non-opaque meningococci occurs in a manner distinct from Opa protein-mediated association. In particular, the amino-terminal domain of CEACAM1 is necessary, but not sufficient for Opa protein-independent binding, which requires multiple extracellular domains of the human receptor in a cellular context. Knock-down of CEACAM1 interferes with binding to lung epithelial cells, whereas chemical or pharmacological disruption of host protein glycosylation does not abrogate CEACAM1 recognition by non-opaque meningococci. The previously characterized meningococcal invasins NadA or Opc do not operate in a CEACAM1-dependent manner.
  
  
  CONCLUSIONS
  The results demonstrate a mechanistically distinct, Opa protein-independent interaction between N. meningitidis and human CEACAM1. Our functional investigations suggest the presence of a second CEACAM1-binding invasin on the meningococcal surface that associates with the protein backbone and not the carbohydrate structures of CEACAM1. The redundancy in meningococcal CEACAM1-binding factors further highlights the important role of CEACAM recognition in the biology of this human-adapted pathogen.
authors.affiliation: Lehrstuhl für Zellbiologie, Universität Konstanz, Konstanz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kuespert
authors.forename: Alexandra
authors.initials: A
authors.lastname: Roth
authors.forename: Christof R
authors.initials: CR
authors.lastname: Hauck
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000502:physiology; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009345:Neisseria meningitidis / Q000502:physiology*; D011485:Protein Binding
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C050308:opacity proteins