toward Persistence in the CF Lung , Based on a Genome

The impaired mucociliary clearance in individuals with Cystic Fibrosis (CF) enables opportunistic pathogens to colonize CF lungs. Here we show that Rothia mucilaginosa is a common CF opportunist that was present in 83% of our patient cohort, almost as prevalent as Pseudomonas aeruginosa (89%). Sequencing of lung microbial metagenomes identified unique R. mucilaginosa strains in each patient, presumably due to evolution within the lung. The de novo assembly of a near-complete R. mucilaginosa (CF1E) genome illuminated a number of potential physiological adaptations to the CF lung, including antibiotic resistance, utilization of extracellular lactate, and modification of the type I restriction-modification system. Metabolic characteristics predicted from the metagenomes suggested R. mucilaginosa have adapted to live within the microaerophilic surface of the mucus layer in CF lungs. The results also highlight the remarkable evolutionary and ecological similarities of many CF pathogens; further examination of these similarities has the potential to guide patient care and treatment. Citation: Lim YW, Schmieder R, Haynes M, Furlan M, Matthews TD, et al. (2013) Mechanistic Model of Rothia mucilaginosa Adaptation oward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data. PLoS ONE 8(5): e64285. doi:10.1371/journal.pone.0064285 Editor: James L. Kreindler, Abramson Research Center, United States of America Received November 30, 2012; Accepted April 13, 2013; Published May 30, 2013 Copyright: 2013 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Institutes of Health and Cystic Foundation Research Inc. through grants (1 R01 GM095384-01 and CFRI #09002) awarded to Forest Rohwer and grant U54 AI065359 awarded to Christopher Hayes and David Low. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ylim@rohan.sdsu.edu ¤ Current address: DOE Joint Genome Institute, Walnut Creek, California, United States of America