“Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions”

Renan F Domingos,Amane Paldes Gonçales,Silvio A Vasconcellos,Monica L Vieira,Ana L T O Nascimento,Eliete C Romero,Zenaide M De Morais

doi:10.1186/1471-2180-12-50

Renan F Domingos, Amane Paldes Gonçales + Show 5 more

Open Access

https://doi.org/10.1186/1471-2180-12-50

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Abstract

BackgroundLeptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp.ResultsWe show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a KD of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG.ConclusionsWe believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro.

Highlights

Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira
Recombinant protein Lsa25 is recognized by antibodies of confirmed cases of leptospirosis To examine whether LIC11834 and LIC12253 leptospiral coding sequences are able to elicit an immune response from an infected host, we evaluated the reactivity of the recombinant proteins Lsa25 and Lsa33 with antibodies present in serum samples of early (MAT -) and convalescent (MAT +) phases of leptospirosis patients
We have described that plasmin - coated virulent L.interrogans bacteria were capable to degrade purified extracellular matrix components fibronectin [19] and laminin (Vieira et al, unpublished data), a step that may contribute for dissemination of the bacteria through the host tissues

Summary

Introduction

Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. L. interrogans serovar Copenhageni genome annotation identified many unknown coding sequences predicted to be surface exposed proteins. Characterization of these proteins, with no previously assigned function, should increase our understanding of this intriguing pathogen’s biology. Lsa can interact to PLG and both proteins bind the complement regulator of the classical pathway C4bp. We believe that these proteins are likely to be involved in Leptospira host interactions

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