Identification of leptospiral proteases involved in immune evasion mechanisms from the human complement system.

Author(s)

Tatiana Rodrigues Fraga

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2014-08-01

Examining board members

Lourdes Isaac; Cristiane Rodrigues Guzzo Carvalho; Fernanda Calheta Vieira Portaro; Edimara da Silva Reis; Aline Maria da Silva

• Advisor: Lourdes Isaac; Ângela Silva Barbosa

Abstract

Leptospirosis is a zoonotic disease caused by pathogenic Leptospira. To establish the infection, these bacteria have developed strategies to escape the complement system. In this work, we demonstrate that culture supernatant from pathogenic Leptospira is capable of inhibiting the three complement pathways. We observe that this supernatant possess proteolytic activity under C3, C3b and iC3b, FB (alternative pathway), C2 and C4b (classical and lectin pathways). The proteins C3, C4, C2 and FB were also cleaved when normal human serum (NHS) was used as a source of complement. We demonstrate that these proteases act together with the host regulators Factor I and Factor H in C3b cleavage. The cleavages were inhibited by 1,10-phenanthroline, suggesting the involvement of metalloproteinases. Leptospira metalloproteinases from the thermolysin family were produced as recombinant proteins and cleaved C3 in NHS. We concluded that proteases from pathogenic Leptospira can inactivate complement molecules and are potential targets for new therapies in leptospirosis. (AU)

• FAPESP's process: 09/11714-9 - Identification of leptospiral proteases involved with scape mechanisms from the human complement system.
• Grantee: Tatiana Rodrigues Fraga
• Support Opportunities: Scholarships in Brazil - Doctorate