title: Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum.
abstract: Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules present in pathogenic but not in saprophytic Leptospira species. We have previously shown that Lig proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L. biflexa serovar Patoc as a surrogate host to address the specific role of LigA and LigB proteins in leptospiral complement evasion. L. biflexa expressing LigA or LigB was able to acquire FH and C4BP. Bound complement regulators retained their cofactor activities of FI in the proteolytic cleavage of C3b and C4b. Moreover, heterologous expression of ligA and ligB genes in the saprophyte L. biflexa enhanced bacterial survival in human serum. Complement deposition on lig-transformed L. biflexa was assessed by flow cytometry analysis. With regard to MAC deposition, L. biflexa expressing LigA or LigB presented an intermediate profile: MAC deposition levels were greater than those found in the pathogenic L. interrogans, but lower than those observed for L. biflexa wildtype. In conclusion, Lig proteins contribute to in vitro control of complement activation on the leptospiral surface, promoting an increased bacterial survival in human serum.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Castiblanco-Valencia
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: Fraga
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Leandro C D
authors.initials: LC
authors.lastname: Breda
authors.affiliation: Faculty of Veterinary Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Sílvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Cláudio P
authors.initials: CP
authors.lastname: Figueira
authors.affiliation: Institut Pasteur, Biology of Spirochetes Unit, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Picardeau
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale University, EUA, CT, USA.
authors.forename: Elsio
authors.initials: E
authors.lastname: Wunder
authors.affiliation: Oswaldo Cruz Foundation, Salvador, Bahia, Brazil; Department of Epidemiology of Microbial Diseases, Yale University, EUA, CT, USA.
authors.forename: Albert I
authors.initials: AI
authors.lastname: Ko
authors.affiliation: Laboratory of Bacteriology, Butantan Institute, São Paulo, Brazil.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Barbosa
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: louisaac@icb.usp.br.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D017244:Complement Factor I / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000276:immunology; D020387:Food Chain; D006801:Humans; D057131:Immune Evasion; D007919:Leptospira / Q000472:pathogenicity / Q000502:physiology*; D007922:Leptospirosis / Q000276:immunology*; D011485:Protein Binding
chemical_list: D000942:Antigens, Bacterial; D015938:Complement Membrane Attack Complex; C487005:LigA-m protein, Leptospira interrogans; C487006:LigB-m protein, Leptospira interrogans; D003179:Complement C3b; D015935:Complement C4b; D017242:Complement Factor H; D017244:Complement Factor I
keywords: C4BP; Complement; Factor H; Immune evasion; Leptospira; Lig proteins