title: Inactivation of the Moraxella catarrhalis 7169 ferric uptake regulator increases susceptibility to the bactericidal activity of normal human sera.
abstract: Moraxella catarrhalis is a strict human pathogen and a significant cause of respiratory disease and otitis media. In direct response to these infections, research efforts have focused primarily on the identification of potential vaccine targets. The general biology of M. catarrhalis, however, including the mechanisms utilized to survive in the human host, remains poorly understood. Previous work has demonstrated that M. catarrhalis expresses iron-repressible proteins, suggesting the presence of iron acquisition systems under the control of a ferric uptake regulator (Fur). In this study M. catarrhalis fur has been cloned and sequenced from strain 7169. A deletion-insertion mutation of 7169 fur resulted in upregulation of iron-repressible outer membrane proteins in the absence and presence of iron. This mutant strain, 7169fur1, was significantly more sensitive to the bactericidal activity of normal human serum than the resistant wild-type strain. These data suggest that constitutive expression of iron-regulated proteins may provide multiple targets for human antibodies. In addition, the 7169 fur mutant provides an important tool for further investigation of the iron acquisition mechanisms utilized by M. catarrhalis.
authors.affiliation: Department of Microbiology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Furano
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Campagnari
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001770:Blood Bactericidal Activity; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D016870:Neisseriaceae Infections / Q000382:microbiology; D010033:Otitis Media / Q000382:microbiology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron