A novel cell-binding mechanism of Moraxella catarrhalis ubiquitous surface protein UspA: specific targeting of the N-domain of carcinoembryonic antigen-related cell adhesion molecules by UspA1.
Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are receptors for several Neisseria and Haemophilus spp. In this investigation, we demonstrate that a major outer membrane protein of Moraxella catarrhalis (Mx) strains, belonging to the ubiquitous surface protein (Usp) family, also interacts with the receptor. The interaction was demonstrated in Western blot overlay of SDS-PAGE-separated bacterial proteins using soluble receptor constructs as well as by co-precipitation experiments. The identity of the bacterial ligand was further ascertained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). It was shown to belong to the UspA1 subfamily. In general, antibodies raised against synthetic UspA1, but not UspA2, peptides bound to the Mx ligand. CEACAM1-Fc-binding property could be demonstrated in all the clinical isolates examined but varied between strains. A single colony derivative of an Mx isolate was also demonstrated to bind to transfected Chinese hamster ovary and some human respiratory epithelial cells in a CEACAM-dependent manner. Thus, we have identified the third respiratory pathogen with the capacity to target the CEACAM family of receptors. The Mx ligand is structurally unrelated to those of Neisseria and Haemophilus.
Hill
Darryl J
DJ
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Virji
Mumtaz
M
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D015153:Blotting, Western; D016466:CHO Cells; D015815:Cell Adhesion Molecules; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D001936:Moraxella catarrhalis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001426:Bacterial Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006360:Heat-Shock Proteins; C078564:universal stress protein A, Bacteria