title: Role of the oligopeptide permease ABC Transporter of Moraxella catarrhalis in nutrient acquisition and persistence in the respiratory tract.
abstract: Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wild-type M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires l-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract.
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Jones
authors.affiliation: Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Department of Structural Biology, University at Buffalo, The 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: Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kirkham
authors.affiliation: Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Brauer
authors.affiliation: Department of Structural Biology, University at Buffalo, The 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: Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York, USA Division of Infectious Diseases, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, New York, USA murphyt@buffalo.edu.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D001936:Moraxella catarrhalis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D045828:Moraxellaceae Infections / Q000382:microbiology*; D005810:Multigene Family; D009154:Mutation; D011994:Recombinant Proteins; D012141:Respiratory Tract Infections / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; C037230:oligopeptide permease, Bacteria