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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 11 NOV 27 2013.
• Citações Web of Science: 33

Resumo

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)

• Processo FAPESP: 11/07297-3 - Colonização e evasão ao sistema complemento do hospedeiro por Leptospira: I. Caracterização funcional do fator de elongação Tu (EF-Tu) II. Interação com vitronectina humana
• Beneficiário: Angela Silva Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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