cystic fibrosis
Minireview | Host-Microbe BiologyEcological Succession of Polymicrobial Communities in the Cystic Fibrosis AirwaysAntimicrobial therapies against cystic fibrosis (CF) lung infections are largely aimed at the traditional, well-studied CF pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex, despite the fact that the CF lung harbors a complex and dynamic polymicrobial community. A clinical...
Research Article | Clinical Science and EpidemiologyHigh-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic TherapySubjects with cystic fibrosis battle polymicrobial lung infections throughout their lifetime. Although antibiotic therapy is a principal treatment for CF lung disease, we have little understanding of how antibiotics affect the CF lung microbiome and metabolome and how much the community changes on daily timescales. By analyzing 594 longitudinal CF sputum samples from six adult subjects, we show that the sputum microbiome and metabolome...
Research Article | Ecological and Evolutionary ScienceLying in Wait: Modeling the Control of Bacterial Infections via Antibiotic-Induced ProvirusesAntibiotic resistance is a growing concern for management of common bacterial infections. Here, we show that antibiotics can be effective at subinhibitory levels when bacteria carry latent phage. Our findings suggest that specific treatment strategies based on the identification of latent viruses in individual bacterial strains may be an effective personalized medicine approach to antibiotic stewardship.
Research Article | Host-Microbe BiologyMolecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic FibrosisMicrobial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same...
Research Article | Host-Microbe BiologyTemperate Bacteriophages from Chronic Pseudomonas aeruginosa Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial SusceptibilityPseudomonas aeruginosa is a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance...
Research Article | Novel Systems Biology TechniquesMetabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen DominanceCystic fibrosis (CF) is a genetic disease in which chronic airway infections and lung inflammation result in respiratory failure. CF airway infections are usually caused by bacterial communities that are difficult to eradicate with available antibiotics. Using species abundance data for clinically stable adult CF patients assimilated from three published studies, we developed a metabolic model of CF airway communities to better...
Research Article | Ecological and Evolutionary ScienceMetapopulation Structure of CRISPR-Cas Immunity in Pseudomonas aeruginosa and Its VirusesPseudomonas aeruginosa is a widespread opportunistic pathogen and a major cause of morbidity and mortality in cystic fibrosis patients. Microbe-virus interactions play a critical role in shaping microbial populations, as viral infections can kill microbial populations or contribute to gene flow among microbes. Investigating how...
Research Article | Ecological and Evolutionary ScienceBalance Trees Reveal Microbial Niche DifferentiationBy explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss .
Editor's Pick Research Article | Ecological and Evolutionary ScienceLong-Term Evolution of Burkholderia multivorans during a Chronic Cystic Fibrosis Infection Reveals Shifting Forces of SelectionBacteria may become genetically and phenotypically diverse during long-term colonization of cystic fibrosis (CF) patient lungs, yet our understanding of within-host evolutionary processes during these infections is lacking. Here we combined current genome sequencing technologies and detailed phenotypic profiling of the opportunistic pathogen Burkholderia multivorans...