Functional characterization of LcpA, a surface-exposed protein of Leptospira spp. that binds the human complement regulator C4BP.
We have previously shown that pathogenic leptospiral strains are able to bind C4b binding protein (C4BP). Surface-bound C4BP retains its cofactor activity, indicating that acquisition of this complement regulator may contribute to leptospiral serum resistance. In the present study, the abilities of seven recombinant putative leptospiral outer membrane proteins to interact with C4BP were evaluated. The protein encoded by LIC11947 interacted with this human complement regulator in a dose-dependent manner. The cofactor activity of C4BP bound to immobilized recombinant LIC11947 (rLIC11947) was confirmed by detecting factor I-mediated cleavage of C4b. rLIC11947 was therefore named LcpA (for leptospiral complement regulator-acquiring protein A). LcpA was shown to be an outer membrane protein by using immunoelectron microscopy, cell surface proteolysis, and Triton X-114 fractionation. The gene coding for LcpA is conserved among pathogenic leptospiral strains. This is the first characterization of a Leptospira surface protein that binds to the human complement regulator C4BP in a manner that allows this important regulator to control complement system activation mediated either by the classical pathway or by the lectin pathway. This newly identified protein may play a role in immune evasion by Leptospira spp. and may therefore represent a target for the development of a human vaccine against leptospirosis.
Barbosa
Angela S
AS
Laboratório de Bacteriologia, Instituto Butantan, Avenida Vital Brazil, São Paulo, Brazil. angelabarbosa@butantan.gov.br
Monaris
Denize
D
Silva
Ludmila B
LB
Morais
Zenaide M
ZM
Vasconcellos
Sílvio A
SA
Cianciarullo
Aurora M
AM
Isaac
Lourdes
L
Abreu
Patricia A E
PA
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D003001:Cloning, Molecular; D050716:Complement C4b-Binding Protein; D004797:Enzyme-Linked Immunosorbent Assay; D005798:Genes, Bacterial / Q000235:genetics / Q000502:physiology; D006649:Histocompatibility Antigens; D006801:Humans; D015151:Immunoblotting; D007919:Leptospira / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007921:Leptospira interrogans / Q000276:immunology; D007922:Leptospirosis / Q000382:microbiology*; D016253:Microscopy, Immunoelectron; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins
D001425:Bacterial Outer Membrane Proteins; C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens; D011994:Recombinant Proteins
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