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Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism

Summary

This study investigated why some strains of the fungus Aspergillus terreus are resistant to amphotericin B, an important antifungal medicine. Researchers compared a resistant strain with a mutated version that became susceptible to the drug. They found that certain genes called P-type ATPases are more active in resistant strains and may help the fungus pump ions and alter its cell membrane to survive the drug. Additionally, mutations in genes responsible for producing secondary metabolites were linked to the visible changes seen when fungal cultures degenerate.

Background

Aspergillus terreus exhibits intrinsic resistance to amphotericin B (AmB), a critical antifungal drug. Culture degeneration in A. terreus leads to the emergence of sectorized morphologies with altered antifungal susceptibility profiles. This study investigates the molecular mechanisms underlying AmB resistance in wild-type versus sectorized strains.

Objective

To characterize the molecular and phenotypic differences between an AmB-resistant wild-type (WT) A. terreus strain and its AmB-susceptible sectorized derivative (ATSec) to elucidate genes involved in AmB resistance mechanisms.

Results

P-type ATPase genes were significantly over-expressed in AmB-resistant WT compared to ATSec in response to AmB treatment. Polyketide synthase (PKS) genes showed higher expression in WT control versus ATSec, with ATSec carrying exclusive mutations in PKS-related genes. No significant differences in sterol content or virulence were observed between strains.

Conclusion

P-type ATPases likely contribute to AmB resistance through ion transport and phospholipid membrane composition alterations. Mutations in polyketide synthesis pathways may be key drivers of the sectorized phenotype. These findings suggest potential drug targets for novel antifungal therapies and mechanisms underlying culture degeneration in fungi.
  • Published in:mBio,
  • Study Type:Experimental Study,
  • Source: PMID: 39998230; DOI: 10.1128/mbio.03926-24
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