Interaction of Leptospira Elongation Factor Tu with Plasminogen and Complement Factor H: A Metabolic Leptospiral Protein with Moonlighting Activities

Author(s)

Wolff, Danielly G. ^[1] ; Castiblanco-Valencia, Monica M. ^[2] ; Abe, Cecilia M. ^[3] ; Monaris, Denize ^[1] ; Morais, Zenaide M. ^[4] ; Souza, Gisele O. ^[4] ; Vasconcellos, Silvio A. ^[4] ; Isaac, Lourdes ^[2] ; Abreu, Patricia A. E. ^[1] ; Barbosa, Angela S. ^[1]

Affiliation

^[1] Inst Butantan, Lab Bacteriol, 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] Univ Sao Paulo, Fac Med Vet & Zootecnia, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 11 NOV 27 2013.
• Web of Science Citations: 33

Abstract

The elongation factor Tu (EF-Tu), an abundant bacterial protein involved in protein synthesis, has been shown to display moonlighting activities. Known to perform more than one function at different times or in different places, it IS found in several subcellular locations in a single organism, and may serve as a virulence factor in a range of important human pathogens. Here we demonstrate that Leptospira EF-Tu is surface-exposed and performs additional roles as a cell-surface receptor for host plasma proteins. It binds plasminogen in a dose-dependent manner, and lysine residues are critical for this interaction. Bound plasminogen is converted to active plasm in, which in turn, is able to cleave the natural substrates C3b and fibrinogen. Leptospira EF-Tu also acquires the complement regulator Factor H (FH). FH bound to immobilized EF-Tu displays cofactor activity, mediating C3b degradation by Factor I (FI). In this manner, EF-Tu may contribute to leptospiral tissue invasion and complement inactivation. To our knowledge this is the first description of a leptospiral protein exhibiting moonlighting activities. (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