Review Article

Paracoccidioides Spp.: Virulence Factors and Immune-Evasion Strategies

Table 4

Paracoccidioides spp. genes shown by functional molecular studies using antisense technology to be involved in virulence and/or immune-evasion strategies from the host.

GeneEncodesBiological roleReferences

PbCDC42Rho GTPase(i) Coordination of cell growth/morphogenesis of
yeast cells, promoting an enhanced ability
to evade the host immune system.

PbHAD32Hydrolase(i) Adhesin involved in initial attachment of the infectious
particles to the lungs.
[80, 81]

PbAOXOxidase part of the electron transport
chain in mitochondria
(i) Essential during the establishment of the fungal infection,
possibly by assisting redox balancing during cell growth
and the morphological switch.
[151, 152, 154]

PbHSP90Molecular chaperone(i) Binds and stabilizes calcineurin thus controlling the
cell differentiation.
(ii) Essential upon thermo-dependent response and
oxidative injury promoting fungal adaptation to the host.

PbGP43Cell-surface component(i) Adhesin that inhibits the phagocytic and fungicidal
capacity of macrophages, through binding to mannose
receptors and inducing IL-18 production.
[73, 76, 106, 107]
(ii) Ability to reduce nitric oxide levels.
(iii) Adherence receptor in the internalization of the yeast
into the host cell altering its cytoskeleton structure.
(iv) Modulation of host cells apoptosis.

PbP27Protein mainly localized in cytoplasm
and cell wall of yeast cells
(i) Involved in the yeast cellular morphological and
glucose metabolism.
(ii) Possible role in promoting latency in the host.

PbRbt5Surface glycosylphosphatidylinositol-
(GPI-) anchored protein
(i) Hemoglobin uptake as an iron source for
intracellular survival.
(ii) Potential virulence factor.

PbCCPCytochrome c oxidase(i) Avoids cell damage caused by nitrosative and oxidative stress.[148, 150]
(ii) Promote fungal survival within macrophages.
(iii) Potential virulence factor.

PbSOD1Cytosolic superoxide dismutase(i) Defense against endogenous-produced ROS.[155]

PbSOD3Extracellular superoxide dismutase(i) Pronounced extracellular activity involved in combating
superoxide radicals generated during the
host-pathogen interaction.
(ii) Potential virulence factor.

Pb14-3-330 kDa protein(i) Adhesin able to bind laminin.[105107]
(ii) Critical role in attachment/infection to host components
and fungal virulence.
(iii) Involved in the morphological switching, ergosterol
biosynthesis, and modulating apoptosis of host phagocytic
and epithelial cells.

PbSCONCMember of the Toll-like receptor family
encoding a negative regulator of the
inorganic sulfur assimilation pathway
(i) Dimorphism regulator by modulating the inorganic
sulfur metabolism and influencing virulence.
(ii) Novel virulence determinant.

PbCATACatalases(i) Major role in endogenous ROS homeostasis in
Paracoccidioides cells.

PbCATPCatalases(i) Mainly triggered in the presence of exogenous ROS and
highly relevant for fungal virulence.