Pathogenic Leptospira Species Acquire Factor H and Vitronectin via the Surface Protein LcpA

Author(s):Show less -

da Silva, Ludmila Bezerra ^[1] ; Miragaia, Lidia dos Santos ^[1] ; Dantas Breda, Leandro Carvalho ^[2] ; Abe, Cecilia Mari ^[3] ; Braga Schmidt, Mariana Costa ^[4] ; Moro, Ana Maria ^[4] ; Monaris, Denize ^[1] ; Conde, Jonas Nascimento ^[5] ; Jozsi, Mihaly ^[6] ; Isaac, Lourdes ^[2] ; Estima Abreu, Patricia Antonia ^[1] ; Barbosa, Angela Silva ^[1]

Affiliation

^[1] Inst Butantan, Bacteriol Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil

^[3] Inst Butantan, Lab Biol Celular, Sao Paulo - Brazil

^[4] Inst Butantan, Lab Biofarmacos Celulas Anim, Sao Paulo - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Genom Estrutural, BR-21941 Rio De Janeiro - Brazil

^[6] Eotvos Lorand Univ, Dept Immunol, MTA ELTE Lendulet Complement Res Grp, Budapest - Hungary

• Document type: Journal article
• Source: Infection and Immunity; v. 83, n. 3, p. 888-897, MAR 2015.
• Web of Science Citations: 18

Abstract

Upon infection, pathogenic Leptospira species bind several complement regulators in order to overcome host innate immunity. We previously characterized a 20-kDa leptospiral surface protein which interacts with C4b binding protein (C4BP): leptospiral complement regulator-acquiring protein A (LcpA). Here we show that LcpA also interacts with human factor H (FH), which remains functionally active once bound to the protein. Antibodies directed against short consensus repeat 20 (SCR20) inhibited binding of FH to LcpA by approximately 90%, thus confirming that this particular domain is involved in the interaction. We have also shown for the first time that leptospires bind human vitronectin and that the interaction is mediated by LcpA. Coincubation with heparin blocked LcpA-vitronectin interaction in a dose-dependent manner, strongly suggesting that binding may occur through the heparin binding domains of vitronectin. LcpA also bound to the terminal pathway component C9 and inhibited Zn2+-induced polymerization and membrane attack complex (MAC) formation. Competitive binding assays indicated that LcpA interacts with C4BP, FH, and vitronectin through distinct sites. Taken together, our findings indicate that LcpA may play a role in leptospiral immune evasion. (AU)

• FAPESP's process: 11/07297-3 - Colonization and evasion of host complement system by Leptospira: I. Functional characterization of the Elongation Factor Tu (EF-Tu) II. Interaction with human vitronectin
• Grantee: Angela Silva Barbosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/50043-0 - Complement system and pathogenicity of Leptospires: mechanisms of activation and evasion, identification of bacterial ligands, characterization of proteases and establishment of an in vivo murine model
• Grantee: Lourdes Isaac
• Support Opportunities: Research Projects - Thematic Grants