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Adaptation Under Pressure: Resistance and Stress Response Interplay in Clinical Aspergillus fumigatus Isolates

Ivana Segéňová1, Ján Víglaš1, Tomáš Pagáč1

  • 1Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, 812 37 Bratislava, Slovakia.

Journal of Fungi (Basel, Switzerland)
|June 25, 2025
PubMed

Insights

This study reveals that Aspergillus fumigatus uses non-genetic survival strategies like persister cells and stress adaptation, impacting antifungal treatment efficacy. Targeting stress pathways offers a promising approach to combat fungal infections.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Fungal Pathogenesis

Background:

  • Understanding Aspergillus fumigatus survival mechanisms is crucial for effective antifungal therapies.
  • Antifungal resistance, stress adaptation, and virulence are key factors influencing treatment outcomes.

Purpose of the Study:

  • Investigate resistance profiles, stress responses, and survival strategies of clinical Aspergillus fumigatus isolates.
  • Identify non-genetic survival mechanisms and their impact on antifungal efficacy.
  • Evaluate the potential of targeting stress response pathways to enhance antifungal treatment.

Main Methods:

  • Analysis of six clinical Aspergillus fumigatus isolates from the Czech Republic.
  • Determination of resistance profiles and stress response profiling.
  • In vitro and in vivo (Galleria mellonella) assays to assess survival, virulence, and treatment efficacy.

Main Results:

  • Azole-susceptible strains formed persister cells under supra-MIC concentrations, indicating a non-genetic survival mechanism.
  • Principal component analysis showed that azole-resistant strains may rely on signal transduction pathways for survival.
  • Combinatorial treatment with posaconazole and dithiothreitol improved antifungal efficacy.
  • Azole resistance conferred a competitive disadvantage in azole-free environments.
  • In vivo virulence was strain-specific and did not directly correlate with resistance.

Conclusions:

  • Fungal survival is multifactorial, with stress adaptation, tolerance, and persistence significantly impacting treatment outcomes.
  • Non-classical resistance mechanisms, such as persister cell formation, play a vital role in fungal survival.
  • Targeting stress response pathways is a promising strategy to enhance current antifungal agents and manage Aspergillus fumigatus resistance.
Keywords:
Aspergillus fumigatusazolesfitness costpersistenceresistancestress responsetolerancevirulence

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