Identification of a hemin utilization protein of Moraxella catarrhalis (HumA).
Moraxella catarrhalis is a major cause of acute otitis media in young children and has also been implicated as an important cause of exacerbations in adults with underlying pulmonary disease. Due to the considerable level of antibiotic resistance and the high degree of carriage rates in young children, it is likely that the incidence of M. catarrhalis infections will continue to rise. M. catarrhalis is a strict human respiratory pathogen, and this bacterium uses both transferrin and lactoferrin receptors to fulfill the essential iron requirement for survival in vivo. However, these are the only described iron acquisition systems for this organism. In this report we have demonstrated that M. catarrhalis can also utilize hemin as a sole source of iron for growth. In addition, we have identified and characterized an outer membrane protein with homology (26 to 28% similarity) to other known hemin binding and uptake proteins in related gram-negative organisms (i.e., Bordetella and Yersinia spp.). This newly described M. catarrhalis protein, termed HumA, is capable of directly binding to hemin coupled to a solid-phase matrix. M. catarrhalis HumA expressed on the surface of an Escherichia coli hemA-deficient strain (K-12 EB53) is fully capable of complementing the defect and thus restoring the ability of this strain to grow in the presence of hemin. When M. catarrhalis is grown in the presence of hemin, HumA expression is clearly increased as shown by Western blotting with polyclonal antiserum developed against a HumA peptide. In addition, growth analyses revealed that a HumA-deficient mutant of M. catarrhalis (7169::humA) is restricted for growth in the presence of hemin as the sole iron source compared to the wild-type strain. We conclude that HumA is an essential component of a hemin uptake and utilization system previously undescribed for M. catarrhalis, thus providing another mechanism of iron acquisition that may facilitate persistent colonization of the mucosal surface.
Furano
Kristin
K
Department of Microbiology and Immunology, State University of New York at Buffalo, 14214, USA.
Campagnari
Anthony A
AA
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D016296:Mutagenesis; D017422:Sequence Analysis, DNA
D001425:Bacterial Outer Membrane Proteins; D006427:Hemin