Journal article
Paracoccidioides brasiliensis Enolase Is a Surface Protein That Binds Plasminogen and Mediates Interaction of Yeast Forms with Host Cells
Infection and immunity, Vol.78(9), pp.4040-4050
09/2010
Handle:
https://hdl.handle.net/2376/111351
PMCID: PMC2937444
PMID: 20605975
Abstract
Paracoccidioidomycosis (PCM), caused by the dimorphic fungus
Paracoccidioides brasiliensis
, is a disseminated, systemic disorder that involves the lungs and other organs. The ability of the pathogen to interact with host components, including extracellular matrix (ECM) proteins, is essential to further colonization, invasion, and growth. Previously, enolase (EC 4.2.1.11) was characterized as a fibronectin binding protein in
P. brasiliensis
. Interaction of surface-bound enolase with plasminogen has been incriminated in tissue invasion for pathogenesis in several pathogens. In this paper, enolase was expressed in
Escherichia coli
as a recombinant glutathione
S
-transferase (GST) fusion protein (recombinant
P. brasiliensis
enolase [r
Pb
Eno]). The
P. brasiliensis
native enolase (
Pb
Eno) was detected at the fungus surface and cytoplasm by immunofluorescence with an anti-r
Pb
Eno antibody. Immobilized purified r
Pb
Eno bound plasminogen in a specific, concentration-dependent fashion. Both native enolase and r
Pb
Eno activated conversion of plasminogen to plasmin through tissue plasminogen activator. The association between
Pb
Eno and plasminogen was lysine dependent. In competition experiments, purified r
Pb
Eno, in its soluble form, inhibited plasminogen binding to fixed
P. brasiliensis
, suggesting that this interaction required surface-localized
Pb
Eno. Plasminogen-coated
P. brasiliensis
yeast cells were capable of degrading purified fibronectin, providing
in vitro
evidence for the generation of active plasmin on the fungus surface. Exposure of epithelial cells and phagocytes to enolase was associated with an increased expression of surface sites of adhesion. In fact, the association of
P. brasiliensis
with epithelial cells and phagocytes was increased in the presence of r
Pb
Eno. The expression of
Pb
Eno was upregulated in yeast cells derived from mouse-infected tissues. These data indicate that surface-associated
Pb
Eno may contribute to the pathogenesis of
P. brasiliensis
.
Metrics
11 Record Views
Details
- Title
- Paracoccidioides brasiliensis Enolase Is a Surface Protein That Binds Plasminogen and Mediates Interaction of Yeast Forms with Host Cells
- Creators
- Sarah Veloso Nogueira - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilFernanda L Fonseca - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilMarcio L Rodrigues - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilVasanth Mundodi - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilErika A Abi-Chacra - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilMichael S Winters - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilJohn F Alderete - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, BrazilCélia Maria de Almeida Soares - Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001-970 Goiânia, Goiás, Brazil
- Publication Details
- Infection and immunity, Vol.78(9), pp.4040-4050
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900547664601842
- Language
- English
- Resource Type
- Journal article