Identification and functional characterisation of Complement Regulator Acquiring Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4.
BACKGROUND
B. burgdorferi sensu lato (sl) is the etiological agent of Lyme borreliosis in humans. Spirochetes have adapted themselves to the human immune system in many distinct ways. One important immune escape mechanism for evading complement activation is the binding of complement regulators Factor H (CFH) or Factor H-like protein1 (FHL-1) to Complement Regulator-Acquiring Surface Proteins (CRASPs).


RESULTS
We demonstrate that B. garinii OspA serotype 4 (ST4) PBi resist complement-mediated killing by binding of FHL-1. To identify the primary ligands of FHL-1 four CspA orthologs from B. garinii ST4 PBi were cloned and tested for binding to human CFH and FHL-1. Orthologs BGA66 and BGA71 were found to be able to bind both complement regulators but with different intensities. In addition, all CspA orthologs were tested for binding to mammalian and avian CFH. Distinct orthologs were able to bind to CFH of different animal origins.


CONCLUSIONS
B. garinii ST4 PBi is able to evade complement killing and it can bind FHL-1 to membrane expressed proteins. Recombinant proteins BGA66 can bind FHL-1 and human CFH, while BGA71 can bind only FHL-1. All recombinant CspA orthologs from B. garinii ST4 PBi can bind CFH from different animal origins. This partly explains the wide variety of animals that can be infected by B. garinii.
van Burgel
Nathalie D
ND
Department of Medical Microbiology, Centre of Infectious Diseases, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands. n.d.van_burgel@lumc.nl
Kraiczy
Peter
P
Schuijt
Tim J
TJ
Zipfel
Peter F
PF
van Dam
Alje P
AP
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins; D001428:Bacterial Vaccines / Q000235:genetics / Q000378:metabolism*; D015748:Borrelia burgdorferi Group / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008193:Lyme Disease / Q000382:microbiology*; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D015938:Complement Membrane Attack Complex; D008074:Lipoproteins; D008565:Membrane Proteins; C072045:OspA protein; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D017242:Complement Factor H