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

Summary

When Aspergillus terreus fungi are grown in laboratory conditions for extended periods, they sometimes undergo changes that make them look different and behave differently. Scientists found that these changed strains become more susceptible to amphotericin B, a common antifungal drug. By studying the genes and proteins in both the original and changed strains, researchers discovered that special proteins called P-type ATPases appear to be responsible for the fungus’s natural resistance to this drug, offering new targets for developing better antifungal treatments.

Background

Aspergillus terreus is clinically important due to its intrinsic resistance to amphotericin B (AmB), with 36.8% of isolates globally being resistant. Prolonged cultivation of A. terreus on drug-free medium leads to morphological degeneration marked by the emergence of fluffy mycelium-type sectors that show altered antifungal susceptibility profiles. This study investigates how sectorization changes AmB resistance mechanisms in A. terreus.

Objective

The study aimed to characterize an AmB-resistant wild-type (WT) strain and its AmB-susceptible sectorized derivative (ATSec) to elucidate the genes involved in AmB resistance. Gene expression levels and whole-genome sequencing were compared between WT and ATSec with and without AmB treatment to identify molecular mechanisms underlying the resistance phenotype.

Results

P-type ATPase genes were significantly over-expressed in AmB-treated WT compared to ATSec, suggesting involvement in AmB resistance. Polyketide synthase genes showed ATSec-exclusive mutations and up-regulation in control WT, suggesting a role in sectorization phenotype. No significant differences were found in sterol content between WT and ATSec, despite sterol’s known role in AmB interactions.

Conclusion

P-type ATPases appear to play a significant role in AmB resistance in A. terreus through ion transport and potential phospholipid membrane composition changes. Mutations in polyketide synthesis genes contribute to the sectorization phenotype. Further investigation is needed to confirm these mechanisms and explore P-type ATPase inhibition as a potential therapeutic strategy.
  • Published in:mBio,
  • Study Type:Experimental Laboratory Study,
  • Source: PMID: 39998230, DOI: 10.1128/mbio.03926-24
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