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Paracoccidioides lutzii Infects Galleria mellonella Employing Formamidase as a Virulence Factor

Elisa Dias Pereira1, Thalison Rodrigues Moreira1, Vanessa Rafaela Milhomem Cruz-Leite1

  • 1Department of Biochemistry and Molecular Biology, Institute of Biological Sciences II, Federal University of Goiás, Goiânia, Brazil.

Plos Neglected Tropical Diseases
|September 3, 2024
PubMed

Insights

Formamidase is crucial for Paracoccidioides lutzii pathogenicity. Silencing this enzyme in P. lutzii reduced fungal virulence and immune stimulation in Galleria mellonella larvae, establishing it as a key virulence factor.

Area of Science:

  • Mycology
  • Pathogen Biology
  • Immunology

Background:

  • Formamidase (FMD) is vital for fungal growth, releasing nitrogen.
  • FMD is upregulated in Paracoccidioides under starvation and infection.
  • The role of P. lutzii formamidase as a virulence factor is undefined.

Purpose of the Study:

  • To investigate the role of formamidase in P. lutzii pathogenicity.
  • To determine if formamidase influences immune stimulation and virulence in vivo.

Main Methods:

  • Infection of Galleria mellonella larvae with an fmd-silenced P. lutzii strain.
  • Assessment of fungal burden, melanogenesis, and nodule formation.
  • Evaluation of larval survival rates.

Main Results:

  • Formamidase silencing led to improper nodule arrangement and reduced melanogenesis.
  • A significant decrease in fungal burden was observed in fmd-silenced P. lutzii infections.
  • Larval survival rate doubled when infected with the fmd-silenced strain.

Conclusions:

  • Formamidase is implicated in P. lutzii's molecular recognition by Galleria immune cells.
  • Formamidase silencing attenuates P. lutzii pathogenicity in vivo.
  • This study establishes formamidase as a P. lutzii virulence factor.

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