Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism
ABSTRACT Prolonged cultivation of certain filamentous fungi, including Aspergillus terreus, on drug-free medium leads to degeneration and morphological heterogeneity, marked by the emergence of fluffy mycelium-type sectors. This phenomenon may indicate alterations in antifungal susceptibility profil...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2025-04-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03926-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850185252655333376 |
|---|---|
| author | David Eisele Michael Blatzer Anna Maria Dietl Ulrike Binder Christoph Müller Ferry Hagen Tongta Sae-Ong Sascha Schäuble Gianni Panagiotou Roya Vahedi-Shahandashti Cornelia Lass-Flörl |
| author_facet | David Eisele Michael Blatzer Anna Maria Dietl Ulrike Binder Christoph Müller Ferry Hagen Tongta Sae-Ong Sascha Schäuble Gianni Panagiotou Roya Vahedi-Shahandashti Cornelia Lass-Flörl |
| author_sort | David Eisele |
| collection | DOAJ |
| description | ABSTRACT Prolonged cultivation of certain filamentous fungi, including Aspergillus terreus, on drug-free medium leads to degeneration and morphological heterogeneity, marked by the emergence of fluffy mycelium-type sectors. This phenomenon may indicate alterations in antifungal susceptibility profiles (particularly to amphotericin B (AmB) in A. terreus), as well as reductions or losses in conidiation, sexuality, secondary metabolite production, and/or virulence. In the present study, various characteristics of an AmB-resistant wild-type (WT) strain and its AmB-susceptible sectorized derivative (ATSec) were characterized. Compared to WT, ATSec exhibited increased susceptibility to AmB, reduced sporulation, and comparable sterol contents and virulence in Galleria mellonella. To elucidate the genes involved in AmB resistance, gene expression levels were compared between WT and ATSec with and without AmB treatment. The expression of P-type ATPase-related genes, which are implicated in membrane composition changes and consequently in AmB resistance, was significantly higher in the WT strain compared to ATSec. Moreover, the up-regulation of genes involved in the biosynthesis of polyketides—a diverse group of secondary metabolites—was higher in WT compared to ATSec, with a significant number of these genes also carrying at least one mutation. The findings of this study indicate that P-type ATPases may significantly be involved in AmB susceptibility and resistance observed in ATSec and WT strains. Additionally, mutations in polyketide synthase genes in ATSec may contribute to the phenotypic alterations associated with the sectorized phenotype.IMPORTANCEProlonged cultivation of certain filamentous fungi, including Aspergillus terreus, on drug-free medium leads to degeneration and morphological heterogeneity, marked by the emergence of fluffy mycelium-type sectors. This phenomenon may indicate alterations in antifungal susceptibility profiles (particularly to amphotericin B (AmB) in A. terreus), as well as reductions or losses in conidiation, sexuality, secondary metabolite production, and/or virulence. In the present study, various characteristics of an AmB-resistant wild-type strain (WT) and its AmB-susceptible sectorized derivative (ATSec) were characterized. Compared to WT, ATSec exhibited increased susceptibility to AmB, reduced sporulation, and comparable sterol contents and virulence in Galleria mellonella. To elucidate the genes involved in AmB resistance, gene expression levels were compared between WT and ATSec with and without AmB treatment. The expression of P-type ATPase-related genes, which are implicated in membrane composition changes and consequently in AmB resistance, was significantly higher in the WT strain compared to ATSec. Moreover, the up-regulation of genes involved in the biosynthesis of polyketides - a diverse group of secondary metabolites - was higher in WT compared to ATSec, with a significant number of these genes also carrying at least one mutation. The findings of this study indicate that P-type ATPases may significantly be involved in AmB susceptibility and resistance observed in ATSec and WT strains. Additionally, mutations in polyketide synthase genes in ATSec may contribute to the phenotypic alterations associated with the sectorized phenotype. |
| format | Article |
| id | doaj-art-45768d58665a42b2af3af7ead3388e0f |
| institution | OA Journals |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-45768d58665a42b2af3af7ead3388e0f2025-08-20T02:16:46ZengAmerican Society for MicrobiologymBio2150-75112025-04-0116410.1128/mbio.03926-24Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanismDavid Eisele0Michael Blatzer1Anna Maria Dietl2Ulrike Binder3Christoph Müller4Ferry Hagen5Tongta Sae-Ong6Sascha Schäuble7Gianni Panagiotou8Roya Vahedi-Shahandashti9Cornelia Lass-Flörl10Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Medical Mycology, Westerdijk Fungal Biodiversity Institute (WI-KNAW), Utrecht, the NetherlandsDepartment of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI), Jena, GermanyDepartment of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI), Jena, GermanyDepartment of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI), Jena, GermanyInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaABSTRACT Prolonged cultivation of certain filamentous fungi, including Aspergillus terreus, on drug-free medium leads to degeneration and morphological heterogeneity, marked by the emergence of fluffy mycelium-type sectors. This phenomenon may indicate alterations in antifungal susceptibility profiles (particularly to amphotericin B (AmB) in A. terreus), as well as reductions or losses in conidiation, sexuality, secondary metabolite production, and/or virulence. In the present study, various characteristics of an AmB-resistant wild-type (WT) strain and its AmB-susceptible sectorized derivative (ATSec) were characterized. Compared to WT, ATSec exhibited increased susceptibility to AmB, reduced sporulation, and comparable sterol contents and virulence in Galleria mellonella. To elucidate the genes involved in AmB resistance, gene expression levels were compared between WT and ATSec with and without AmB treatment. The expression of P-type ATPase-related genes, which are implicated in membrane composition changes and consequently in AmB resistance, was significantly higher in the WT strain compared to ATSec. Moreover, the up-regulation of genes involved in the biosynthesis of polyketides—a diverse group of secondary metabolites—was higher in WT compared to ATSec, with a significant number of these genes also carrying at least one mutation. The findings of this study indicate that P-type ATPases may significantly be involved in AmB susceptibility and resistance observed in ATSec and WT strains. Additionally, mutations in polyketide synthase genes in ATSec may contribute to the phenotypic alterations associated with the sectorized phenotype.IMPORTANCEProlonged cultivation of certain filamentous fungi, including Aspergillus terreus, on drug-free medium leads to degeneration and morphological heterogeneity, marked by the emergence of fluffy mycelium-type sectors. This phenomenon may indicate alterations in antifungal susceptibility profiles (particularly to amphotericin B (AmB) in A. terreus), as well as reductions or losses in conidiation, sexuality, secondary metabolite production, and/or virulence. In the present study, various characteristics of an AmB-resistant wild-type strain (WT) and its AmB-susceptible sectorized derivative (ATSec) were characterized. Compared to WT, ATSec exhibited increased susceptibility to AmB, reduced sporulation, and comparable sterol contents and virulence in Galleria mellonella. To elucidate the genes involved in AmB resistance, gene expression levels were compared between WT and ATSec with and without AmB treatment. The expression of P-type ATPase-related genes, which are implicated in membrane composition changes and consequently in AmB resistance, was significantly higher in the WT strain compared to ATSec. Moreover, the up-regulation of genes involved in the biosynthesis of polyketides - a diverse group of secondary metabolites - was higher in WT compared to ATSec, with a significant number of these genes also carrying at least one mutation. The findings of this study indicate that P-type ATPases may significantly be involved in AmB susceptibility and resistance observed in ATSec and WT strains. Additionally, mutations in polyketide synthase genes in ATSec may contribute to the phenotypic alterations associated with the sectorized phenotype.https://journals.asm.org/doi/10.1128/mbio.03926-24Aspergillus terreusP-type ATPaseamphotericin B (AmB) resistanceculture degenerationsectorizationphenotypic heterogeneity |
| spellingShingle | David Eisele Michael Blatzer Anna Maria Dietl Ulrike Binder Christoph Müller Ferry Hagen Tongta Sae-Ong Sascha Schäuble Gianni Panagiotou Roya Vahedi-Shahandashti Cornelia Lass-Flörl Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism mBio Aspergillus terreus P-type ATPase amphotericin B (AmB) resistance culture degeneration sectorization phenotypic heterogeneity |
| title | Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism |
| title_full | Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism |
| title_fullStr | Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism |
| title_full_unstemmed | Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism |
| title_short | Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism |
| title_sort | aspergillus terreus sectorization a morphological phenomenon shedding light on amphotericin b resistance mechanism |
| topic | Aspergillus terreus P-type ATPase amphotericin B (AmB) resistance culture degeneration sectorization phenotypic heterogeneity |
| url | https://journals.asm.org/doi/10.1128/mbio.03926-24 |
| work_keys_str_mv | AT davideisele aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT michaelblatzer aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT annamariadietl aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT ulrikebinder aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT christophmuller aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT ferryhagen aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT tongtasaeong aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT saschaschauble aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT giannipanagiotou aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT royavahedishahandashti aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism AT cornelialassflorl aspergillusterreussectorizationamorphologicalphenomenonsheddinglightonamphotericinbresistancemechanism |