Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 548071
Title Data from: Relevance of heterokaryosis for adaptation and azole-resistance development in Aspergillus fumigatus
Author(s) Zhang, J.; Snelders, E.; Zwaan, B.J.; Schoustra, S.E.; Kuijper, Ed J.; Arendrup, Maiken C.; Melchers, Willem J.G.; Verweij, Paul E.; Debets, A.J.M.
DOI https://doi.org/10.5061/dryad.fr3kt2d
Department(s) Laboratory of Genetics
PE&RC
Publication type Dataset
Publication year 2019
Keyword(s) heterokaryon incompatibility - azole resistance - flexible nuclear ratio - Aspergillus fumigatus
Abstract Aspergillus fumigatus causes a range of diseases in humans, some of which are characterized by fungal persistence. A. fumigatus, being a generalist saprotroph, may initially establish lung colonisation 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 Aspergillus diseases, such as cystic fibrosis and chronic pulmonary aspergillosis, A. fumigatus 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 A. fumigatus. We found evidence for heterokaryosis of A. fumigatus in patients with chronic Aspergillus 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.
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