Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans

Autor(es)

Breda, Leandro C. D. ^[1] ; Hsieh, Ching-Lin ^[2] ; Castiblanco Valencia, Monica M. ^[1] ; da Silva, Ludmila B. ^[3] ; Barbosa, Angela S. ^[3] ; Blom, Anna M. ^[4] ; Yung-Fu, Chang ; Isaac, Lourdes ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 - USA

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

^[4] Lund Univ, Dept Translat Med, Div Med Prot Chem, Malmo - Sweden

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 9, n. 10 OCT 2015.
• Citações Web of Science: 11

Resumo

The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H {[}FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP alpha-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins. (AU)

• Processo FAPESP: 11/14347-7 - Mecanismos de evasão do sistema complemento por Leptospira spp: Interação com o inibidor de C1 esterase e C4BP.
• Beneficiário: Leandro Carvalho Dantas Breda
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/50043-0 - Sistema complemento e patogenicidade de leptospiras: mecanismos de ativação e escape identificação de ligantes bacterianos, caracterização de proteases e estabelecimento de modelo murino in vivo
• Beneficiário: Lourdes Isaac
• Modalidade de apoio: Auxílio à Pesquisa - Temático