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Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis

A J Almeida1, C Cunha, J A Carmona

  • 1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

Fungal Genetics and Biology : FG & B
|August 19, 2009
PubMed

Insights

Investigating Paracoccidioides brasiliensis, researchers found that reducing Cdc42 protein levels decreased cell size and polymorphism. This led to increased phagocytosis and reduced virulence, highlighting Cdc42

Area of Science:

  • Mycology
  • Cell Biology
  • Infectious Diseases

Background:

  • Paracoccidioides brasiliensis exhibits significant cell size and shape variability (polymorphism) and multiple budding, impacting its pathogenesis.
  • Cdc42 is a crucial protein regulating polarized growth in various cell types and is implicated in fungal pathogenesis.

Purpose of the Study:

  • To investigate the role of Cdc42 in the cell growth and virulence of the yeast-form of Paracoccidioides brasiliensis.
  • To understand the contribution of cell morphology and size to P. brasiliensis pathogenesis.

Main Methods:

  • Antisense technology was employed to reduce the expression of PbCDC42 in P. brasiliensis yeast cells.
  • The effects of reduced PbCDC42 expression on cell size, growth homogeneity, phagocytosis, and virulence in a mouse model were evaluated.

Main Results:

  • Knock-down of PbCDC42 resulted in smaller, more homogenous P. brasiliensis cells, altering the wild-type's characteristic polymorphism.
  • Reduced PbCDC42 expression led to increased susceptibility to phagocytosis by host immune cells.
  • The virulence of P. brasiliensis in a mouse infection model was significantly decreased with lower PbCDC42 levels.

Conclusions:

  • Pbcdc42p is a key protein in the host-pathogen interactions of Paracoccidioides brasiliensis.
  • The polymorphic nature and variable cell size of P. brasiliensis are important factors contributing to its pathogenesis.
  • Targeting PbCDC42 may represent a potential strategy for controlling P. brasiliensis infections.

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