{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:13:45Z","timestamp":1788311625693,"version":"build-2803163510"},"reference-count":54,"publisher":"The Royal Society","issue":"1896","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Proc. R. Soc. B."],"published-print":{"date-parts":[[2019,2,13]]},"abstract":"<jats:p>\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            causes a range of diseases in humans, some of which are characterized by fungal persistence.\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            , being a generalist saprotroph, may initially establish lung colonization due to its physiological versatility and subsequently adapt through genetic changes to the human lung environment and antifungal treatments. Human lung-adapted genotypes can arise by spontaneous mutation and\/or recombination and subsequent selection of the fittest genotypes. Sexual and asexual spores are considered crucial contributors to the genetic diversity and adaptive potential of aspergilli by recombination and mutation supply, respectively. However, in certain\n            <jats:italic>Aspergillus<\/jats:italic>\n            diseases, such as cystic fibrosis and chronic pulmonary aspergillosis,\n            <jats:italic>A. fumigatus<\/jats:italic>\n            may not sporulate but persist as a network of fungal mycelium. During azole therapy, such mycelia may develop patient-acquired resistance and become heterokaryotic by mutations in one of the nuclei. We investigated the relevance of heterokaryosis for azole-resistance development in\n            <jats:italic>A. fumigatus.<\/jats:italic>\n            We found evidence for heterokaryosis of\n            <jats:italic>A. fumigatus<\/jats:italic>\n            in patients with chronic\n            <jats:italic>Aspergillus<\/jats:italic>\n            diseases. Mycelium from patient-tissue biopsies segregated different homokaryons, from which heterokaryons could be reconstructed. Whereas all variant homokaryons recovered from the same patient were capable of forming a heterokaryon, those from different patients were heterokaryon-incompatible. We furthermore compared heterokaryons and heterozygous diploids constructed from environmental isolates with different levels of azole resistance. When exposed to azole, the heterokaryons revealed remarkable shifts in their nuclear ratio, and the resistance level of heterokaryons exceeded that of the corresponding heterozygous diploids.\n          <\/jats:p>","DOI":"10.1098\/rspb.2018.2886","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T08:20:05Z","timestamp":1550046005000},"page":"20182886","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Relevance of heterokaryosis for adaptation and azole-resistance development in\n            <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1098","volume":"286","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-9375","authenticated-orcid":true,"given":"Jianhua","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline E.","family":"Snelders","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas J.","family":"Zwaan","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-5539","authenticated-orcid":true,"given":"Sijmen E.","family":"Schoustra","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed J.","family":"Kuijper","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiken C.","family":"Arendrup","sequence":"additional","affiliation":[{"name":"Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark"},{"name":"Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J. G.","family":"Melchers","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Centre of Expertise in Mycology Radboudumc\/CWZ, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Centre of Expertise in Mycology Radboudumc\/CWZ, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1799-4617","authenticated-orcid":true,"given":"Alfons J. 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