Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs.
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.
Alitalo
Antti
A
Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, and Peptide and Protein Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
Meri
Taru
T
Lankinen
Hilkka
H
Seppälä
Ilkka
I
Lahdenne
Pekka
P
Hefty
P Scott
PS
Akins
Darrin
D
Meri
Seppo
S
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
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