Mechanistic Model of Rothia mucilaginosa Adaptation toward Persistence in the CF Lung, Based on a Genome Reconstructed from Metagenomic Data

Yan Wei Lim, Robert Schmieder, Matthew Haynes, Mike Furlan, T. David Matthews, Katrine Whiteson, Stephen J. Poole, Christopher S. Hayes, David A. Low, Heather Maughan, Robert Edwards, Douglas Conrad, Forest Rohwer

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.