title: Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein.
abstract: 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.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. edilaniaraujo@gmail.com.
authors.forename: Edilânia Gomes Araújo
authors.initials: EG
authors.lastname: Chaves
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. weberblood@gmail.com.
authors.forename: Simone Schneider
authors.initials: SS
authors.lastname: Weber
authors.affiliation: Laboratório de Microscopia, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil. snbao2009@gmail.com.
authors.forename: Sonia Nair
authors.initials: SN
authors.lastname: Báo
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. luiz.bmolecular@gmail.com.
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Pereira
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. alexandre.bailao@gmail.com.
authors.forename: Alexandre Melo
authors.initials: AM
authors.lastname: Bailão
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. clbluiz2@gmail.com.
authors.forename: Clayton Luiz
authors.initials: CL
authors.lastname: Borges
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil. cmasoares@gmail.com.
authors.forename: Célia Maria de Almeida
authors.initials: CM
authors.lastname: Soares
mesh_terms: D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D010228:Paracoccidioides / Q000201:enzymology* / Q000235:genetics; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D040901:Proteomics / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D005337:Fibrin; D010958:Plasminogen; D005341:Fibrinolysin; D005634:Fructose-Bisphosphate Aldolase