title: The specificity of protection against cationic antimicrobial peptides by lactoferrin binding protein B.
abstract: A variety of Gram-negative pathogens possess host-specific lactoferrin (Lf) receptors that mediate the acquisition of iron from host Lf. The integral membrane protein component of the receptor, lactoferrin binding protein A specifically binds host Lf and is required for acquisition of iron from Lf. In contrast, the role of the bi-lobed surface lipoprotein, lactoferrin binding protein B (LbpB), in Lf binding and iron acquisition is uncertain. A common feature of LbpBs from most species is the presence of clusters of negatively charged amino acids in the protein's C-terminal lobe. Recently it has been shown that the negatively charged regions from the Neisseria meningitidis LbpB are responsible for protecting against an 11 amino acid cationic antimicrobial peptide (CAP), lactoferricin (Lfcin), derived from human Lf. In this study we investigated whether the LbpB confers resistance to other CAPs since N. meningitidis is likely to encounter other CAPs from the host. LbpB provided protection against the cathelicidin derived peptide, cathelicidin related antimicrobial peptide (mCRAMP), but did not confer protection against Tritrp 1 or LL37 under our experimental conditions. When tested against a range of rationally designed synthetic peptides, LbpB was shown to protect against IDR-1002 and IDR-0018 but not against HH-2 or HHC10.
authors.affiliation: Departments of Microbiology, Immunology & Infectious Diseases and Biochemistry & Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: Ari
authors.initials: A
authors.lastname: Morgenthau
authors.forename: Sarathy K
authors.initials: SK
authors.lastname: Partha
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; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054804:Cathelicidins / Q000037:antagonists & inhibitors; D058507:Host Specificity; D006801:Humans; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D002352:Carrier Proteins; D054804:Cathelicidins; C490098:LTF protein, human; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; C027768:lactoferrin binding proteins, bacterial; C038340:lactoferrin receptors; C082171:lactoferricin B; D007501:Iron; D007781:Lactoferrin; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases