A. fumigatus uses parasex to create genetic variation in the lung of chronically colonized patients

What is it about?

We tested our hypothesis that genetic variation in chronic biofilms can be created through parasexual recombination by phenotypic and genetic analysis of A. fumigatus isolates cultured from patients with cystic fibrosis (CF), chronic pulmonary lung disease, acute invasive aspergillosis, and from the environment. As diploids are the hallmark of parasex, and diploid spores are larger, we screened isolates 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 characterize diploid associated genetic variation. We identified diploids in six of 11 (55%) CF patients and from 1 of 24 (4%) chronic aspergillosis patients, but not in isolates from acute infection and the environment which indicates that chronic colonization facilitates the parasexual cycle. Furthermore, we showed that diploid formation was associated with accumulation of mutations and variable haploid offspring including a voriconazole-resistant isolate.

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Why is it important?

Our findings provide explanations how A. fumigatus can adapt and persist in CF patients although confided to a hyphal state during many years. This adaptation potential explains observed phenotypic changes and in-host acquired azole resistance in A. fumigatus isolates of chronically colonized patients. Our findings will be useful for understanding the genetics and biology of A. fumigatus in the human lung, especially for persistent chronically colonized patients.

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