Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein
Carregando...
Data
2015
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
Background: Despite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic
mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express
molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic
activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix
components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that
Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic
activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using
proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to
plasminogen.
Results: In the present study, we employed proteomic analysis of the secretome, in order to identify
plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome,
presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with
the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the
protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding
protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen
and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as
demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing
the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA.
These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/
dissemination of Paracoccidioides.
Conclusions: These data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding
proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might
be involved somehow in the processes of invasion and spread of the fungus during infection.
Descrição
Palavras-chave
Fructose 1,6-bisphosphate aldolase, Paracoccidioides, Proteome, Secretome, Plasminogen-binding proteins
Citação
CHAVES, Edilânia Gomes Araújo et al. Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein. BMC Microbiology, London, v. 15, n. 53, 2015.