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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Immune Evasion by Pathogenic Leptospira Strains: The Secretion of Proteases that Directly Cleave Complement Proteins

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Author(s):
Fraga, Tatiana Rodrigues [1] ; Courrol, Daniella dos Santos [1] ; Castiblanco-Valencia, Monica Marcela [1] ; Hirata, Izaura Yoshico [2] ; Vasconcellos, Slvio Arruda [2] ; Juliano, Luiz [3] ; Barbosa, Angela Silva [4] ; Isaac, Lourdes [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Vet Med, BR-05508900 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[4] Butantan Inst, Lab Bacteriol, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Journal of Infectious Diseases; v. 209, n. 6, p. 876-886, MAR 15 2014.
Web of Science Citations: 33
Abstract

Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved alpha and beta chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis. (AU)

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