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

Danielly G Wolff,Denize Monaris,Mónica M Castiblanco-Valencia,Zenaide M Morais,Gisele O Souza,Patrícia A E Abreu,Angela S Barbosa,Cecília M Abe,Sílvio A Vasconcellos,Lourdes Isaac,Antonio Carlos Seguro

doi:10.1371/journal.pone.0081818

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.

Highlights

Pathogenic microorganisms are able to penetrate and colonize host tissues by establishing complex interactions with host molecules
Laminin-1 and collagen Type IV were derived from the basement membrane of EngelbrethHolm-Swarm mouse sarcoma, cellular fibronectin was derived from human foreskin fibroblasts, plasma fibronectin was isolated from human plasma, collagen Type I was isolated from rat tail, and elastin from human aorta
Our results revealed that elongation factor Tu (EF-Tu) was recognized by anti-EF-Tu mouse serum (Figure 1A)

Summary

Introduction

Pathogenic microorganisms are able to penetrate and colonize host tissues by establishing complex interactions with host molecules. Surface proteins mediate binding of microbial pathogens to an array of host targets such as cell receptors, extracellular matrix components, coagulation cascade molecules and complement regulators. This process enables pathogens to disseminate to multiple organs and to evade hosts innate immune response. Recent reports have attributed unexpected functions to cytosolic bacterial proteins normally involved in key metabolic processes or in the cell stress response (reviewed in 1). By performing diverse cellular functions related to adhesion, invasion and modulation of the host immune system, this intriguing class of proteins may contribute to virulence of important pathogens [1,2]. Molecular chaperones and proteins involved in protein synthesis may perform multiple functions in some microorganisms [1]

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Conclusion