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Infect Immun. 2015 Nov 23;84(2):432-8. doi: 10.1128/IAI.00799-15. Print 2016 Feb.

The Vaccine Candidate Substrate Binding Protein SBP2 Plays a Key Role in Arginine Uptake, Which Is Required for Growth of Moraxella catarrhalis.

Author information

1
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.
2
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.
3
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.

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.

PMID:
26597985
PMCID:
PMC4730574
DOI:
10.1128/IAI.00799-15
[Indexed for MEDLINE]
Free PMC Article

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