Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation

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Microbial cells vastly outnumber human cells in our bodies, yet we are only beginning to understand how these microbes influence human health and disease. One disease for which microbial communities are especially important is cystic fibrosis, where persistent lung infections can be lethal. Fungi are associated with poor respiratory function, but how fungal communities change with disease progression or treatment remains enigmatic. Here, we assess the dynamics of fungal communities by combining high-throughput sequencing of sputum samples from 28 patients with detailed analysis of phenotypes and genotypes of 1,603 fungal isolates. We found stable communities dominated by Candida and Aspergillus, and diversity in traits important for host adaptation. Antifungal drug resistance varied largely between species, while morphogenesis varied within species. For Candida species, the capacity to transition between yeast and filaments is a key virulence trait that is normally regulated by inducing cues, however, 28 isolates grew as filaments without such cues. Filamentation was due to loss-of-function mutations in the transcriptional regulator NRG1 in most isolates, which conferred resistance to the filament-repressive effects of a common bacterial pathogen. This work provides a portrait of the fungal microbiome associated with a lethal disease, and illuminates a genetic basis of pathogen adaptation.

Vyšlo v časopise: Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005308
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005308

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