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Amphotericin B Resistance in Aspergillus terreus Is Overpowered by Coapplication of Pro-oxidants

Michael Blatzer1, Emina Jukic1, Wilfried Posch1

  • 11 Division of Hygiene and Medical Microbiology, Medical University of Innsbruck , Innsbruck, Austria .

Antioxidants & Redox Signaling
|June 10, 2015
PubMed
Abstract

Insights

Amphotericin B (AmB) effectiveness against resistant Aspergillus terreus can be restored. Combining AmB with pro-oxidants, which promote reactive oxygen species (ROS), overcomes fungal resistance, offering new treatment strategies.

Area of Science:

  • Mycology
  • Antifungal Drug Discovery
  • Antimicrobial Resistance

Background:

  • Invasive fungal infections are increasing in immunocompromised patients.
  • Amphotericin B (AmB) is a potent antifungal with low resistance rates.
  • Aspergillus terreus often exhibits intrinsic resistance to AmB.

Purpose of the Study:

  • To investigate the mechanism of AmB action in resistant (ATR) and susceptible (ATS) Aspergillus terreus.
  • To explore strategies for overcoming AmB resistance in A. terreus.

Main Methods:

  • Characterization of AmB's mode of action in resistant and susceptible A. terreus isolates.
  • Assessment of cellular redox status and reactive oxygen species (ROS) generation.
  • Evaluation of AmB efficacy in combination with antioxidants and pro-oxidants in vitro and in vivo (Galleria model).

Main Results:

  • AmB induces ROS generation in susceptible A. terreus strains.
  • Resistant A. terreus isolates better manage AmB-induced oxidative stress.
  • Antioxidants increase AmB tolerance in susceptible strains, while pro-oxidants restore AmB susceptibility in resistant strains.

Conclusions:

  • AmB efficacy is modulated by cellular oxidative stress.
  • Combining AmB with pro-oxidants represents a novel therapeutic approach to treat AmB-resistant fungal infections.
  • This strategy offers potential for treating resistant Aspergillus terreus infections.

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