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Alteration of cell wall composition leads to amphotericin B resistance in Aspergillus flavus

K Seo1, H Akiyoshi, Y Ohnishi

  • 1Department of Biological Chemistry, Faculty of Integrated Arts and Sciences, School of Medicine, The University of Tokushima, Japan.

Microbiology and Immunology
|December 28, 1999
PubMed

Insights

Researchers developed amphotericin B (AmB)-resistant Aspergillus flavus by increasing AmB concentrations. The resistance is linked to changes in the fungal cell wall

Area of Science:

  • Mycology
  • Antifungal Resistance
  • Biochemistry

Background:

  • Amphotericin B (AmB) is a crucial antifungal agent.
  • Understanding resistance mechanisms is vital for effective treatment.
  • Aspergillus flavus is an opportunistic fungal pathogen.

Purpose of the Study:

  • To investigate the mechanisms of acquired amphotericin B resistance in Aspergillus flavus.
  • To identify specific changes in the fungal cell wall associated with AmB resistance.

Main Methods:

  • Induction of AmB resistance in Aspergillus flavus through serial transfer on increasing AmB concentrations.
  • Testing cross-resistance to other polyene antibiotics (nystatin, trichomycin).
  • Susceptibility testing of spheroplasts derived from resistant and wild-type strains.
  • Chemical analysis of fungal cell wall components (glucans, proteins).
  • Assessment of AmB adsorption by resistant and wild-type mycelia using SDS treatment.

Main Results:

  • A stable AmB-resistant mutant of Aspergillus flavus was successfully isolated.
  • The acquired resistance was specific to polyene antibiotics.
  • Spheroplasts from resistant strains showed wild-type susceptibility to AmB, indicating cell wall involvement.
  • Resistant mycelia exhibited significantly higher levels of alkali-soluble and -insoluble glucans.
  • AmB adsorption to SDS-treated mycelia was similar between resistant and wild-type strains.

Conclusions:

  • Alterations in the fungal cell wall, particularly increased glucan content, contribute to AmB resistance in Aspergillus flavus.
  • The outermost cell wall layer, potentially involving a 1,3-alpha-glucan and protein complex, plays a key role in resistance.
  • This study provides insights into the biochemical basis of antifungal drug resistance in A. flavus.

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