Analysis of theParacoccidioides brasiliensistriosephosphate isomerase suggests the potential for adhesin function

Abstract

Paracoccidioides brasiliensis is an important fungal pathogen. The disease it causes, paracoccidioidomycosis (PCM), ranges from localized pulmonary infection to systemic processes that endanger the life of the patient. Paracoccidioides brasiliensis adhesion to host tissues contributes to its virulence, but we know relatively little about molecules and the molecular mechanisms governing fungal adhesion to mammalian cells. Triosephosphate isomerase (TPI: EC 5.3.1.1) of P. brasiliensis (PbTPI) is a fungal antigen characterized by microsequencing of peptides. The protein, which is predominantly expressed in the yeast parasitic phase, localizes at the cell wall and in the cytoplasmic compartment. TPI and the respective polyclonal antibody produced against this protein inhibited the interaction of P. brasiliensis to in vitro cultured epithelial cells. TPI binds preferentially to laminin, as determined by peptide inhibition assays. Collectively, these results suggest that TPI is required for interactions between P. brasiliensis and extracellular matrix molecules such as laminin and that this interaction may play an important role in the fungal adherence and invasion of host cells.

A 32-Kilodalton Hydrolase Plays an Important Role in Paracoccidioides brasiliensis Adherence to Host Cells and Influences Pathogenicity

“…Although some P. brasiliensis molecules that may participate in adhesion to host tissues have been identified (e.g., malate synthase, enolase, thriose phosphate isomerase, an adaptinlike protein, and glyceraldehyde-3-phosphate dehydrogenase, among others), the exact role of these proteins remains uncharacterized due to a lack of gene-based evidence (3,4,8,10,26).…”

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

“…The ability to adhere is a biological phenomenon that is widely distributed and shared by many pathogens, enabling the colonization of their respective habitats. 15,16 Some adhesins have been described for P. brasiliensis, such as gp43, 17,18 glyceraldehyde-3-phosphate dehydrogenase, 19 triose phosphate isomerase, 20 enolase, 21,22 a 32-Kda hydrolase, 23,24 malate synthase, 25 isocitrate lyase 26 and the 14-3-3 protein (30 KDa) 27,28 ; this last adhesin is the focus of the present study.…”

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

“…To determine the binding of the recombinant TvTIM proteins (TvTIM1r and TvTIM2r) to Lm, Fn, and Plg, far-Western blotting (FWB) assays were performed as previously described (16), with minor modifications. TvTIM1r and TvTIM2r (1 g) were subjected to SDS-PAGE, blotted onto NC membranes (0.2-m pore size; Bio-Rad), and blocked with 10% nonfat dried milk in PBS-T overnight at 4°C.…”

“…TIM is an important virulence factor when localized to the cellular surfaces of pathogenic organisms. For example, it is an adhesin for epithelial cells and a laminin (Lm)-and Fn-binding protein during the parasitic phase of Paracoccidioides brasiliensis (16). Similarly, TIM is a Plg-binding protein in Staphylococcus aureus (17).…”