Further characterization of complement regulator-acquiring surface proteins of Borrelia burgdorferi.
The three genospecies Borrelia burgdorferi, Borrelia garinii, and Borrelia afzelii, all causative agents of Lyme disease, differ in their susceptibilities to human complement-mediated lysis. We recently reported that serum resistance of borrelias correlates largely with their ability to bind the human complement regulators FHL-1/reconectin and factor H. To date, two complement regulator-acquiring-proteins (CRASP-1 and CRASP-2) have been identified in serum-resistant B. afzelii isolates (P. Kraiczy, C. Skerka, M. Kirschfink, V. Brade, and P. F. Zipfel, Eur. J. Immunol. 31:1674-1684, 2001). Here, we present a comprehensive study of the CRASPs detectable in both serum-resistant and intermediate serum-sensitive B. afzelii and B. burgdorferi isolates. These CRASPs were designated according to the genospecies either as BaCRASPs, when derived from B. afzelii, or as BbCRASPs, for proteins identified in B. burgdorferi isolates. Each borrelial isolate expresses distinct CRASPs that can be differentiated by their mobility and binding phenotypes. A detailed comparison reveals overlapping and even identical binding profiles for BaCRASP-1 (27.5 kDa), BbCRASP-1 (25.9 kDa), and BbCRASP-2 (23.2 kDa), which bind FHL-1/reconectin strongly and interact weakly with factor H. In contrast, two B. afzelii proteins (BaCRASP-4 [19.2 kDa] and BaCRASP-5 [22.5 kDa]) and three B. burgdorferi proteins (BbCRASP-3 [19.8 kDa], BbCRASP-4 [18.5 kDa], and BbCRASP-5 [17.7 kDa]) bind factor H but not FHL-1/reconectin. Most CRASPs bind both human immune regulators at their C-terminal ends. Temperature-dependent up-regulation of CRASPs (BaCRASP-1, BaCRASP-2, and BaCRASP-5) is detected in low-passage borrelias cultured at 33 or 37 degrees C compared with those cultured at 20 degrees C. The characterization of the individual CRASPs on the molecular level is expected to identify new virulence factors and potential vaccine candidates.
Kraiczy
P
P
Institute of Medical Microbiology, University Hospital of Frankfurt, D-60596 Frankfurt, Germany. Kraiczy@em.uni-frankfurt.de
Skerka
C
C
Brade
V
V
Zipfel
P F
PF
D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000276:immunology; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate; D008193:Lyme Disease / Q000209:etiology; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D013696:Temperature
D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D017242:Complement Factor H; D003165:Complement System Proteins