RT Journal Article SR Electronic T1 Parasexual recombination enables Aspergillus fumigatus to persist in cystic fibrosis JF ERJ Open Research JO erjor FD European Respiratory Society SP 00020-2020 DO 10.1183/23120541.00020-2020 A1 Tobias Engel A1 Paul E. Verweij A1 Joost van den Heuvel A1 Dechen Wangmo A1 Jianhua Zhang A1 Alfons J.M. Debets A1 Eveline Snelders YR 2020 UL http://openres.ersjournals.com/content/early/2020/09/17/23120541.00020-2020.abstract AB Aspergillus fumigatus is a saprobic fungus that causes a range of pulmonary diseases, some of which are characterised by fungal persistence such as is observed in cystic fibrosis (CF) patients. Creation of genetic variation is critical for A. fumigatus to adapt to the lung environment, but biofilm formation, especially in CF patients, may preclude mutational supply in A. fumigatus due to its confinement to the hyphal morphotype. We tested our hypothesis that genetic variation is created through parasexual recombination in chronic biofilms by phenotypic and genetic analysis of A. fumigatus isolates cultured from different origins.As diploids are the hallmark of parasex, we screened 799 A. fumigatus isolates obtained from patients with CF, chronic pulmonary lung disease, acute invasive aspergillosis and from the environment for spore size. Benomyl sensitivity, nuclear content measurements through fluorescence activated cell sorting and scanning electron microscopy were used to confirm the diploid state of large size spores. Whole genome sequencing was used to characterise diploid associated genetic variation.We identified 11 diploids in isolates recovered from six of 11 (55%) CF-patients and from one of 24 (4%) chronic aspergillosis patients, but not in 368 isolates from acute infection and the environment. Diploid formation was associated with accumulation of mutations and variable haploid offspring including a voriconazole-resistant isolate.Parasexual recombination allows A. fumigatus to adapt and persist in CF patients, and plays a role in azole resistance development. Our findings are highly significant for understanding the genetics and biology of A. fumigatus in the human lung.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Engel has nothing to disclose.Conflict of interest: Dr. Verweij reports grants from Gilead Sciences, grants from MSD, grants from Pfizer, grants from F2G, non-financial support from OLM, non-financial support from IMMY, outside the submitted work.Conflict of interest: Dr. Van den Heuvel has nothing to disclose.Conflict of interest: Dr. Wangmo has nothing to disclose.Conflict of interest: Dr. Zhang has nothing to disclose.Conflict of interest: Dr. Debets has nothing to disclose.Conflict of interest: Dr. Snelders has nothing to disclose.