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Rho2 regulates granulocyte-triggered stress adaptation and cell wall remodeling in Aspergillus fumigatus

Dominik Ruf1, Kristina Striegler2, Sean Brazil3

  • 1Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Faculty of Medicine, LMU, Munich, Germany.

Microbiological Research
|June 6, 2025
PubMed

Insights

Neutrophil granulocytes activate Aspergillus fumigatus's cell wall integrity pathway. Key components like Rho2 are crucial for fungal survival against immune attacks, highlighting new therapeutic targets.

Area of Science:

  • Mycology
  • Immunology
  • Cell Biology

Background:

  • * Aspergillus fumigatus is an opportunistic fungal pathogen threatening immunocompromised individuals.
  • * Neutrophil granulocytes are critical in combating invasive Aspergillus infections.
  • * Understanding fungal defense mechanisms against immune cells is crucial.

Purpose of the Study:

  • * To investigate how human granulocytes activate the cell wall integrity (CWI) pathway in A. fumigatus.
  • * To elucidate the role of CWI components, specifically Rho2, in fungal survival during immune assault.
  • * To explore the impact of Rho2 modulation on A. fumigatus virulence and cell wall dynamics.

Main Methods:

  • * Investigated A. fumigatus response to human granulocyte attacks.
  • * Analyzed the function of CWI pathway components (MidA, Rho2, Rho4) using mutants.
  • * Assessed fungal virulence in a Galleria mellonella model.
  • * Examined cell wall composition and growth under altered Rho2 expression.
  • * Studied the dependence of Rho2-mediated effects on the CWI MAP kinase MpkA.

Main Results:

  • * Human granulocytes activate the A. fumigatus CWI pathway.
  • * Rho2 and Rho4 are vital for hyphal survival under granulocyte attack.
  • * Rho2 mutants exhibit reduced virulence; Rho2 overexpression enhances resistance to granulocytes.
  • * Constitutive Rho2 activation alters cell wall composition, impairs growth, and depends on MpkA.
  • * Rho2 upregulates cell wall biosynthesis to counteract granulocyte attacks.

Conclusions:

  • * Rho2 is a key mediator of A. fumigatus resistance to neutrophil attacks.
  • * Rho2 strengthens the fungal cell wall by upregulating biosynthesis, aiding survival.
  • * Findings provide insights into fungal immune evasion strategies and potential therapeutic interventions.
Keywords:
Aspergillus fumigatusCell wall integrityGranulocytesMidARho2Rho4

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