{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:03:07Z","timestamp":1785801787156,"version":"3.56.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Austrian Science Fund","award":["W1253-B24"],"award-info":[{"award-number":["W1253-B24"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["210879364"],"award-info":[{"award-number":["210879364"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["210879364"],"award-info":[{"award-number":["210879364"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Prolonged cultivation of certain filamentous fungi, including\n              <jats:italic>Aspergillus terreus<\/jats:italic>\n              , 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\n              <jats:italic>A. terreus<\/jats:italic>\n              ), 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\n              <jats:italic>Galleria mellonella<\/jats:italic>\n              . 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\u2014a diverse group of secondary metabolites\u2014was 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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>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 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03926-24","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T14:08:27Z","timestamp":1740492507000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["<i>Aspergillus terreus<\/i>\n            sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanism"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4428-3241","authenticated-orcid":false,"given":"David","family":"Eisele","sequence":"first","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Blatzer","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]},{"name":"Experimental Neuropathy Unit, Institute Pasteur","place":["Paris, France"]},{"name":"Global Health Department, Institute Pasteur","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Dietl","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Binder","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-1916","authenticated-orcid":true,"given":"Ferry","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Westerdijk Fungal Biodiversity Institute (WI-KNAW)","place":["Utrecht, the Netherlands"]},{"name":"Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam","place":["Amsterdam, the Netherlands"]},{"name":"Department of Medical Microbiology, University Medical Center Utrecht","place":["Utrecht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongta","family":"Sae-Ong","sequence":"additional","affiliation":[{"name":"Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute (Leibniz-HKI)","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Sch\u00e4uble","sequence":"additional","affiliation":[{"name":"Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute (Leibniz-HKI)","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Panagiotou","sequence":"additional","affiliation":[{"name":"Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology \u2013 Hans Kn\u00f6ll Institute (Leibniz-HKI)","place":["Jena, Germany"]},{"name":"Faculty of Biological Sciences, Friedrich Schiller University","place":["Jena, Germany"]},{"name":"Jena University Hospital, Friedrich Schiller University","place":["Jena, Germany"]},{"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-7795","authenticated-orcid":true,"given":"Roya","family":"Vahedi-Shahandashti","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2946-7785","authenticated-orcid":true,"given":"Cornelia","family":"Lass-Fl\u00f6rl","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2002.01682.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-4401-4_10"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.028480"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-023-12615-z"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-008-0026-y"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jip.2021.107588"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00103-13"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmpp.2017.03.009"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004380000335"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00755-17"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2019.103247"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02274-21"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-020-00382-7"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(92)90113-Z"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6220"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01283-12"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1999.tb01231.x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00670-17"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-003-0530-y"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1911-1916.2000"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005171"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.06.007"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007260"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.02048"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-021-11133-0"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycmed.2022.101310"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1354"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00878-16"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605214200"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001871"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13730"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10030112"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0476"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169103"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01384-08"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1788-1796.2004"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1211\/002235702469"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.12.021"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106635"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/ece3.10354"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/gix120"},{"key":"e_1_3_4_44_2","unstructured":"Andrews S. 2010. FastQC a quality control tool for high throughput sequence data."},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv566"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15931.2"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00516"},{"key":"e_1_3_4_50_2","first-page":"1","article-title":"Eucast definitive document E.Def 9.1: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds","volume":"9","author":"Arendrup M","year":"2020","unstructured":"Arendrup M, Meletiadis J, Mouton J, Lagrou K, Hamal P, Guinea J. 2020. Eucast definitive document E.Def 9.1: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. Clin Microbiol Infect 9:1\u201323.","journal-title":"Clin Microbiol Infect"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/014332-0"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051218"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.005"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-00971-x"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty266"},{"key":"e_1_3_4_56_2","unstructured":"Eisele D Sae-Ong T Sch\u00e4uble S Panatgiotou G. 2024. AmB resistant Aspergillus terreus and its AmB susceptible sectorized derivative. Available from: https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1161802"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_3_4_59_2","volume-title":"R: a language and environment for statistical computing","author":"Chambers J","year":"2024","unstructured":"Chambers J, Dalgaard P, Gentleman R, Hornik K, Ihaka R, Kalibera T, Lawrence M, Ligges U, Lumley T, Maechler M, Meyer S, Murrel P, Plummer M, Ripley B, Sarkar D, Temple Lang D, Tierney L, Urbanek S. 2024. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7563.2"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxw041"},{"key":"e_1_3_4_63_2","unstructured":"Van RossumG DrakeFL. 2009. Python 3 reference manual. CreateSpace"},{"key":"e_1_3_4_64_2","unstructured":"Bekatas M Bozarth A Charles E Collonval F Cryan M Darian A Fauske VT Granger B Grout J Krassowski M Klein M Pena-Castellanos G Perez F Presedo-Floyd I Silvester S Tuloup J. 2024. Jupyter-Lab."},{"key":"e_1_3_4_65_2","unstructured":"Anaconda software distribution. 2016. Computer software Anaconda."},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof9080807"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu031"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.23297.2"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02141-2"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac958"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03926-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03926-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T13:04:31Z","timestamp":1744203871000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03926-24"}},"subtitle":[],"editor":[{"given":"Anuradha","family":"Chowdhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":74,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,9]]}},"alternative-id":["10.1128\/mbio.03926-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03926-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]},"assertion":[{"value":"2024-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03926-24"}}