Host-dependent differential expression of factor H binding proteins, their affinity to factor H and complement evasion by Lyme and relapsing fever borreliae.
Binding of complement factor H is crucial for the resistance of Borrelia to complement-mediated lysis. This study was aimed to assess the correlation between the expression of fH binding proteins (FHBPs) during the early phase of infection (48 h after the entry of Borrelia into the blood circulation) and complement resistance of the Borrelia genus. As expected, B. afzelii, B. burgdorferi sensu stricto and B. garinii (Serotype 4, PBi) showed resistance to complement mediated lysis when incubated with human and dog complement, which coincided with the significantly higher expression (P<0.05) of the FHBPs. Similarly, B. coriaceae showed resistance to cattle complement. In non-reservoir hosts borreliae failed to induce expression of FHBPs within 48 h of complement challenge, and did not survive. It is important to note that not only the expression of FHBP but also their binding to fH is required for borrelial resistance to the complement. fH binding may depend on the coiled-coil (CC) motifs observed in the FHBPs, especially at the C terminus. A loss of the C-terminal CC motif in BgCRASP-1 of SKT-1 strain was found in in-silico CC prediction, and may be coupled with SKT-1's inability to bind factor H and evade complement-mediated attack. In contrast, the C-terminal CC motif was observed (P - 1.0) in BgCRASP-1 of PBi that may contributed to its factor H binding and human complement resistance.
Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and pharmacy, Košice, Slovakia.
Lucia
L
Kišová-Vargová
Rastislav
R
Mucha
Dana
D
Cerňanská
Mangesh
M
Bhide
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D015748:Borrelia burgdorferi Group / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012061:Relapsing Fever / Q000276:immunology / Q000382:microbiology; D016415:Sequence Alignment
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017242:Complement Factor H