title: The Vaccine Candidate Substrate Binding Protein SBP2 Plays a Key Role in Arginine Uptake, Which Is Required for Growth of Moraxella catarrhalis.
abstract: Moraxella catarrhalis is an exclusively human pathogen that is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent M. catarrhalis infections would have an enormous global impact in reducing morbidity resulting from these infections. Substrate binding protein 2 (SBP2) of an ABC transporter system has recently been identified as a promising vaccine candidate antigen on the bacterial surface of M. catarrhalis. In this study, we showed that SBP1, -2, and -3 individually bind different basic amino acids with exquisite specificity. We engineered mutants that each expressed a single SBP from this gene cluster and showed in growth experiments that SBP1, -2, and -3 serve a nutritional function through acquisition of amino acids for the bacterium. SBP2 mediates uptake of arginine, a strict growth requirement of M. catarrhalis. Adherence and invasion assays demonstrated that SBP1 and SBP3 play a role in invasion of human respiratory epithelial cells, consistent with a nutritional role in intracellular survival in the human respiratory tract. This work demonstrates that the SBPs of an ABC transporter system function in the uptake of basic amino acids to support growth of M. catarrhalis. The critical role of SBP2 in arginine uptake may contribute to its potential as a vaccine antigen.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA.
authors.forename: Taketo
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kirkham
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Brauer
authors.affiliation: Department of Structural Biology, University at Buffalo, State University of New York, Buffalo, New York, USA Hauptman Woodward Medical Research Institute, Buffalo, New York, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Koszelak-Rosenblum
authors.affiliation: Department of Structural Biology, University at Buffalo, State University of New York, Buffalo, New York, USA Hauptman Woodward Medical Research Institute, Buffalo, New York, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Malkowski
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA murphyt@buffalo.edu.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001120:Arginine / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D001936:Moraxella catarrhalis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D009154:Mutation; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D001120:Arginine