Complement factor H-related proteins & Borrelia
By Linda on Nov 11, 2010 in Infections | comments(0)
Excerpt:
METHODOLOGY/PRINCIPAL FINDINGS: To elucidate whether CRASP-5 and
CRASP-3 interact with various human proteins, both borrelial
proteins were immobilized on magnetic beads. Following incubation
with human serum, bound proteins were eluted and separated by
Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement
regulators CFHR2 and CFHR5 were identified as novel ligands for
both borrelial proteins by employing MALDI-TOF. To further assess
the contributions of CRASP-3 and CRASP-5 to complement
resistance, a serum-sensitive B. garinii strain G1 which lacks
all CFH-binding proteins was used as a valuable model for
functional analyses. Both CRASPs expressed on the B. garinii
outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In
contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only
miniscute amounts of CFH as demonstrated by serum adsorption
assays and FACS analyses. Further functional analysis revealed
that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae
were killed by complement.
CONCLUSIONS/SIGNIFICANCE: In the absence of CFH and the presence
of CFHR1, CFHR2 and CFHR5, assembly and integration of the
membrane attack complex was not efficiently inhibited indicating
that CFH in co-operation with CFHR1,
CFHR2 and CFHR5 supports complement evasion of B. burgdorferi
