title: Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs.
abstract: Borrelia burgdorferi spirochetes can circumvent the vertebrate host's immune system for long periods of time. B. burgdorferi sensu stricto and B. afzelii, but not B. garinii, bind the complement inhibitor factor H to protect themselves against complement-mediated opsonophagocytosis and killing. We found that factor H binding and complement resistance are due to inducible expression of a wide repertoire of outer surface protein E (OspE) lipoproteins variably called OspE, p21, ErpA, and ErpP. Individual Borrelia strains carry multiple plasmid-encoded OspE paralogs. Together the OspE homologs were found to constitute an array of proteins that bind factor H via multiple C-terminal domains that are exposed outwards from the Borrelial surface. Charged residue substitutions in the key binding regions account for variations between OspE family members in the optimal binding pH, temperature, and ionic strength. This may help the spirochetes to adapt into various host environments. Our finding that multiple plasmid-encoded OspE proteins act as virulence factors of Borrelia can provide new tools for the prevention and treatment of borreliosis.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, and Peptide and Protein Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Alitalo
authors.forename: Taru
authors.initials: T
authors.lastname: Meri
authors.forename: Hilkka
authors.initials: H
authors.lastname: Lankinen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.forename: Pekka
authors.initials: P
authors.lastname: Lahdenne
authors.forename: P Scott
authors.initials: PS
authors.lastname: Hefty
authors.forename: Darrin
authors.initials: D
authors.lastname: Akins
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology*; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013987:Ticks / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C493495:CFH protein, human; D008074:Lipoproteins; C084998:OspE protein, Borrelia burgdorferi; D017242:Complement Factor H