title: The role of lactoferrin binding protein B in mediating protection against human lactoferricin.
abstract: Bacteria that inhabit the mucosal surfaces of the respiratory and genitourinary tracts of mammals encounter an iron-deficient environment because of iron sequestration by the host iron-binding proteins transferrin and lactoferrin. Lactoferrin is also present in high concentrations at sites of inflammation where the cationic, antimicrobial peptide lactoferricin is produced by proteolysis of lactoferrin. Several Gram-negative pathogens express a lactoferrin receptor that enables the bacteria to use lactoferrin as an iron source. The receptor is composed of an integral membrane protein, lactoferrin binding protein A (LbpA), and a membrane-bound lipoprotein, lactoferrin binding protein B (LbpB). LbpA is essential for growth with lactoferrin as the sole iron source, whereas the role of LbpB in iron acquisition is not yet known. In this study, we demonstrate that LbpB from 2 different species is capable of providing protection against the killing activity of a human lactoferrin-derived peptide. We investigated the prevalence of lactoferrin receptors in bacteria and examined their sequence diversity. We propose that the protection against the cationic antimicrobial human lactoferrin-derived peptide is associated with clusters of negatively charged amino acids in the C-terminal lobe of LbpB that is a common feature of this protein.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
authors.forename: Ari
authors.initials: A
authors.lastname: Morgenthau
authors.forename: Margaret
authors.initials: M
authors.lastname: Livingstone
authors.forename: Paul
authors.initials: P
authors.lastname: Adamiak
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Schryvers
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D016955:Moraxella bovis / Q000235:genetics; D001936:Moraxella catarrhalis / Q000235:genetics; D009345:Neisseria meningitidis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010446:Peptide Fragments; C027768:lactoferrin binding proteins, bacterial; D007781:Lactoferrin