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

• DOI: 10.1371/journal.ppat.1005308
• Publication Date: 2015-11-20T19:51:03Z
• Authors: Sang Hu Kim; Shawn T. Clark; Anuradha Surendra; Julia K. Copeland; Pauline W. Wang; Ron Ammar; Cathy Collins; D. Elizabeth Tullis; Corey Nislow; David M. Hwang; David S. Guttman; Leah E. Cowen
• Keywords: Host adaptation

The microbiome shapes diverse facets of human biology and disease, with the importance fungi only beginning to be appreciated. Microbial communities infiltrate anatomical sites as respiratory tract healthy humans those diseases such cystic fibrosis, where chronic colonization infection lead clinical decline. Although are frequently recovered from fibrosis patient sputum samples have been associated deterioration lung function, understanding species population dynamics remains in its infancy. Here, we coupled high-throughput sequencing ribosomal RNA internal transcribed spacer 1 (ITS1) phenotypic genotypic analyses 89 28 patients. Fungal defined by were concordant culture-based 1,603 isolates same samples. Different patients harbored distinct fungal communities. There detectable trends, however, including Candida Aspergillus species, which was not perturbed exacerbation or treatment. We identified considerable inter- intra-species variation traits important for host adaptation, antifungal drug resistance morphogenesis. While largely between striking morphogenesis emerged within species. Filamentation uncoupled inducing cues six filamentous resistant filamentation-repressive effects Pseudomonas aeruginosa, implicating inter-kingdom interactions selective force. Genome revealed that all but one mutations transcriptional repressor NRG1; necessary sufficient phenotype. Six independent nrg1 arose different patients, providing a poignant example parallel evolution. Together, this combined clinical-genomic approach provides high-resolution portrait lungs identifies genetic basis pathogen adaptation.