Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis.
Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M. catarrhalis in these populations. Using a genome mining approach we have identified a sulfate binding protein, CysP, of an ATP binding cassette (ABC) transporter system as a novel candidate vaccine antigen. CysP expresses epitopes on the bacterial surface and is highly conserved among strains. Immunization with CysP induces potentially protective immune responses in a murine pulmonary clearance model. In view of these features that indicate CysP is a promising vaccine antigen, we conducted further studies to elucidate its function. These studies demonstrated that CysP binds sulfate and thiosulfate ions, plays a nutritional role for the organism and functions in intracellular survival of M. catarrhalis in human respiratory epithelial cells. The observations that CysP has features of a vaccine antigen and also plays an important role in growth and survival of the organism indicate that CysP is an excellent candidate vaccine antigen to prevent M. catarrhalis otitis media and infections in adults with COPD.
Clinical and Translational Research Center, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA; Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA; Department of Microbiology, University at Buffalo, The State University of New York, 3435 Main Street, Buffalo, NY 14214, USA. Electronic address: murphyt@buffalo.edu.
Timothy F
TF
Murphy
Clinical and Translational Research Center, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA; Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA.
Charmaine
C
Kirkham
Clinical and Translational Research Center, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA; Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA.
Antoinette
A
Johnson
Clinical and Translational Research Center, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA; Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, 875 Ellicott Street, Buffalo, NY 14203, USA.
Aimee L
AL
Brauer
Department of Structural Biology, University at Buffalo, The State University of New York, 700 Ellicott Street, Buffalo, NY 14203, USA; Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA.
Mary
M
Koszelak-Rosenblum
Department of Structural Biology, University at Buffalo, The State University of New York, 700 Ellicott Street, Buffalo, NY 14203, USA; Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA.
Michael G
MG
Malkowski
D000072283:A549 Cells; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D008807:Mice, Inbred BALB C; D001936:Moraxella catarrhalis; D045828:Moraxellaceae Infections / Q000517:prevention & control*; D010033:Otitis Media / Q000517:prevention & control; D033902:Periplasmic Binding Proteins / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000517:prevention & control; D011994:Recombinant Proteins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000517:prevention & control
D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D033902:Periplasmic Binding Proteins; D011994:Recombinant Proteins; C044773:sulfate-binding protein, bacteria
ABC transporter protein; Chronic obstructive pulmonary disease; Moraxella catarrhalis; Otitis media; Substrate binding protein; Vaccine