Catalases of Aspergillus fumigatus

Sophie Paris1, Deborah Wysong, Jean-Paul Debeaupuis

  • 1Unité des Aspergillus, Département Structure et Dynamique des Gènômes, Institut Pasteur, Paris, France. sparis@pasteur.fr

Insights

Aspergillus fumigatus uses catalases to detoxify hydrogen peroxide from host immune cells. While spore catalase is not essential for virulence, mycelial catalases offer transient protection during infection.

Area of Science:

  • Mycology
  • Immunology
  • Biochemistry

Background:

  • Pathogenic fungus *Aspergillus fumigatus* encounters reactive oxygen species (ROS) from host phagocytic cells.
  • Catalases are proposed to detoxify hydrogen peroxide (H₂O₂), a key ROS, aiding fungal survival.
  • *A. fumigatus* produces three catalases: one in conidia and two in mycelia (Cat1p, Cat2p).

Purpose of the Study:

  • To characterize the spore-specific catalase (CatAp) and the second mycelial catalase (Cat2p).
  • To investigate the roles of these catalases in fungal resistance to host defenses and virulence.
  • To analyze the phenotypes of gene-disrupted mutants lacking specific catalases.

Main Methods:

  • Gene disruption to create single and double mutants (e.g., *DeltacatA*, *Deltacat1Deltacat2*).
  • Biochemical characterization of purified catalases (CatAp, Cat2p).
  • Assessment of fungal killing by alveolar macrophages and polymorphonuclear neutrophils.
  • Evaluation of virulence in a rat model of aspergillosis.

Main Results:

  • CatAp is a heat, metal ion, and detergent-resistant dimeric enzyme, homologous to *A. nidulans* CatA and bacterial HPII.
  • *DeltacatA* conidia showed increased H₂O₂ sensitivity but similar macrophage killing and virulence.
  • Cat2p is a heat, metal ion, and detergent-sensitive monomeric catalase-peroxidase, homologous to fungal and bacterial catalase-peroxidases.
  • The double *Deltacat1Deltacat2* mutant showed only slightly increased H₂O₂ sensitivity and similar neutrophil killing.
  • The double mutant exhibited delayed infection in a rat model, indicating a role for mycelial catalases in transient protection.

Conclusions:

  • Conidial catalase (CatAp) is not a significant virulence factor for *A. fumigatus*.
  • Mycelial catalases (Cat1p and Cat2p) provide transient protection against host immune responses during infection.
  • Understanding these fungal defense mechanisms can inform strategies against aspergillosis.

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