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

Microbiol Immunol. 1999;43(11):1017-25. doi: 10.1111/j.1348-0421.1999.tb01231.x.

Abstract

An amphotericin B (AmB)-resistant mutant was isolated from a wild-type AmB-susceptible strain of Aspergillus flavus by serial transfer of conidia on agar plates containing stepwise increased concentrations of AmB up to 100 microg ml-1. The acquired resistance of mycelia was specific for polyene-antibiotics AmB, nystatin and trichomycin. Spheroplasts derived from the resistant mycelia were as susceptible to AmB as the wild-type. Chemical analysis of the cell wall revealed that levels of alkali-soluble and -insoluble glucans were significantly higher in the resistant mycelia as compared to those in the wild-type. When resistant mycelia were treated with SDS, they adsorbed as much AmB as wild-type mycelia. These results suggest that alterations in the cell wall components of mycelia, especially 1,3-alpha-glucan and protein complex in the outermost wall layer, lead to AmB resistance in A. flavus.

MeSH terms

  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Aspergillus flavus / chemistry
  • Aspergillus flavus / drug effects*
  • Aspergillus flavus / genetics
  • Aspergillus flavus / metabolism
  • Cell Wall / chemistry
  • Drug Resistance, Microbial
  • Glucans / chemistry
  • Mutation
  • Polysaccharides, Bacterial / analysis
  • Potassium / metabolism
  • Spheroplasts / metabolism
  • Spores, Fungal / metabolism

Substances

  • Antifungal Agents
  • Glucans
  • Polysaccharides, Bacterial
  • Amphotericin B
  • alpha-1,3-glucan
  • Potassium