title: Identification of an outer membrane lipoprotein involved in nasopharyngeal colonization by Moraxella catarrhalis in an animal model.
abstract: Colonization of the human nasopharynx by Moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of M. catarrhalis to human bronchial epithelial (HBE) cells in vitro affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant M. catarrhalis strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate in vitro, in its ability to attach to HBE cells in vitro, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of M. catarrhalis to persist in an animal model.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Joslin
authors.forename: Christine
authors.initials: C
authors.lastname: Pybus
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Evans
authors.forename: Flora
authors.initials: F
authors.lastname: Lichaa
authors.forename: Chad A
authors.initials: CA
authors.lastname: Brautigam
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D002460:Cell Line; D002682:Chinchilla; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D045828:Moraxellaceae Infections / Q000382:microbiology*; D009302:Nasopharyngeal Diseases / Q000382:microbiology*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008565:Membrane Proteins; D010455:Peptides; D011480:Protease Inhibitors; C078167:OMPA outer membrane proteins; C017339:globomycin