Binding of extracellular matrix proteins to Paracoccidioides brasiliensis

Abstract

Adhesion to extracellular matrix (ECM) proteins plays a crucial role in invasive fungal diseases. ECM proteins bind to the surface of Paracoccidioides brasiliensis yeast cells in distinct qualitative patterns. Extracts from Pb18 strain, before (18a) and after animal inoculation (18b), exhibited differential adhesion to ECM components. Pb18b extract had a higher capacity for binding to ECM components than Pb18a. Laminin was the most adherent component for both samples, followed by type I collagen, fibronectin, and type IV collagen for Pb18b. A remarkable difference was seen in the interaction of the two extracts with fibronectin and their fragments. Pb18b extract interacted significantly with the 120-kDa fragment. Ligand affinity binding assays showed that type I collagen recognized two components (47 and 80kDa) and gp43 bound both fibronectin and laminin. The peptide 1 (NLGRDAKRHL) from gp43, with several positively charged amino acids, contributed most to the adhesion of P. brasiliensis to Vero cells. Synthetic peptides derived from peptide YIGRS of laminin or from RGD of both laminin and fibronectin showed the greatest inhibition of adhesion of gp43 to Vero cells. In conclusion, this work provided new molecular details on the interaction between P. brasiliensis and ECM components.

Decreased expression of 14-3-3 inParacoccidioides brasiliensisconfirms its involvement in fungal pathogenesis

“…46 MendesGiannini et al 47 observed a relationship between virulence and adherence to the ECM when comparing several P. brasiliensis isolates that showed different levels of virulence in vivo; the authors demonstrated that the isolate Pb18, which was recently isolated from an animal, had a greater ability to adhere to ECM components. Confirming the results of Andreotti et al, 2005, 27 we demonstrated that low expression of Pb14-3-3 resulted in a reduction of binding to laminin; this interaction was assessed by ELISA, which has greater sensitivity and specificity than the immunoblotting that was performed in the study cited above.…”

Cell surface expression of adhesins for fibronectin correlates with virulence in Sporothrix schenckii

“…Similarly, different authors have reported a positive correlation between adhesion of fungal pathogens and virulence. For example, pathogenic strains of Aspergillus fumigatus bound significantly more fibronectin than non-pathogenic strains (Wasylnka & Moore, 2000) and, among different strains of P. brasiliensis, the most virulent ones showed a stronger adherence to epithelial cells (Mendes-Giannini et al, 2006;Hanna et al, 2000).…”

“…Study of independent isolates of Paracoccidioides brasiliensis revealed that the strains that were more virulent in animals exhibited enhanced adherence to extracellular matrix proteins in vitro (Hanna et al, 2000;Mendes-Giannini et al, 2006). However, to our knowledge such studies have never been conducted for S. schenckii.…”

Diversity in Paracoccidioides brasiliensis . The PbGP43 gene as a genetic marker

“…The initial interest in gp43 was concentrated in its diagnostic value, since the protein moiety yields highly specific and sensitive reactions for diagnosis and prognosis of PCM [26a, 30,31]. However, the importance of gp43 in the host-parasite relationship has later been recognized at the levels of its adhesive properties to extracellular matrix-associated proteins [32,33] and immune protection. Towards this end, a major T-cell epitope has been mapped in peptide P-10, which is protective to mice and represents a vaccine candidate with immunotherapeutic potential use [34][35][36][37].…”