title: Interaction of Leptospira elongation factor Tu with plasminogen and complement factor H: a metabolic leptospiral protein with moonlighting activities.
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 plasmin, 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.
authors: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brasil.
authors: Danielly G
authors: DG
authors: Wolff
authors: Mónica M
authors: MM
authors: Castiblanco-Valencia
authors: Cecília M
authors: CM
authors: Abe
authors: Denize
authors: D
authors: Monaris
authors: Zenaide M
authors: ZM
authors: Morais
authors: Gisele O
authors: GO
authors: Souza
authors: Sílvio A
authors: SA
authors: Vasconcellos
authors: Lourdes
authors: L
authors: Isaac
authors: Patrícia A E
authors: PA
authors: Abreu
authors: Angela S
authors: AS
authors: Barbosa
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D017242:Complement Factor H / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D007113:Immunity, Innate / Q000276:immunology; D007919:Leptospira / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D008239:Lysine / Q000378:metabolism; D010444:Peptide Elongation Factor Tu / Q000737:chemistry / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D017242:Complement Factor H; D010958:Plasminogen; D005341:Fibrinolysin; D010444:Peptide Elongation Factor Tu; D008239:Lysine