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Paracoccidioides brasiliensis enolase is a surface protein that binds plasminogen and mediates interaction of yeast

Sarah Veloso Nogueira1, Fernanda L Fonseca, Marcio L Rodrigues

  • 1Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, 74001-970, Goiânia, Goiás, Brazil.

Infection and Immunity
|July 8, 2010
PubMed

Insights

Paracoccidioides brasiliensis enolase (PbEno) binds plasminogen, aiding fungal invasion and adhesion. This surface-bound enolase promotes pathogen colonization and virulence in Paracoccidioidomycosis (PCM).

Area of Science:

  • Mycology
  • Pathogenesis
  • Molecular Biology

Background:

  • Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides brasiliensis.
  • Fungal interaction with host extracellular matrix (ECM) proteins is crucial for colonization and invasion.
  • Enolase (EC 4.2.1.11) in P. brasiliensis is a known fibronectin-binding protein involved in pathogenesis.

Purpose of the Study:

  • To investigate the role of P. brasiliensis enolase (PbEno) in interacting with host plasminogen.
  • To determine if PbEno contributes to fungal adhesion and tissue invasion.
  • To explore the functional consequences of PbEno-plasminogen interaction in PCM pathogenesis.

Main Methods:

  • Recombinant P. brasiliensis enolase (rPbEno) was expressed in E. coli.
  • Immunofluorescence was used to detect native PbEno on fungal surfaces.
  • Binding assays and enzymatic activity measurements assessed PbEno-plasminogen interactions.
  • Competition experiments and fibronectin degradation assays were performed.
  • Adhesion assays with epithelial cells and phagocytes were conducted.

Main Results:

  • Native PbEno is present on the surface and in the cytoplasm of P. brasiliensis.
  • Immobilized rPbEno specifically bound plasminogen in a concentration-dependent manner.
  • PbEno activated plasminogen to plasmin via tissue plasminogen activator, a lysine-dependent process.
  • Soluble rPbEno inhibited plasminogen binding to the fungus, indicating the importance of surface-localized PbEno.
  • Plasminogen-coated yeast cells degraded fibronectin, and PbEno enhanced fungal adhesion to host cells.
  • PbEno expression was upregulated in yeast cells from infected mouse tissues.

Conclusions:

  • Surface-associated PbEno plays a significant role in P. brasiliensis pathogenesis.
  • The interaction between PbEno and plasminogen facilitates fungal invasion and ECM degradation.
  • PbEno enhances fungal adhesion to host cells, contributing to systemic spread.
  • PbEno is a potential therapeutic target for treating Paracoccidioidomycosis.

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