The Ecological Role of Bacteriophages in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a progressive and inflammatory disease caused by long-term inhalation exposure to respiratory irritants. Sputum samples from COPD patients have a higher-than-average bacterial load present consisting of Proteobacteria, Actinobacteria and Firmicutes. Patients often experience exacerbations and require antibiotics and/or steroids to stabilize their condition, but this is undetermined if these bacterial shifts are commensal or pathogenic. Many of the bacteria found in COPD lungs are multi-drug-resistant and antimicrobial-resistant, leading to persistent infections and degradation of patients' lungs.Bacteriophages are predatory viruses that only infect bacteria and help meditate microbiomes. In the past few decades, bacteriophage presence and their potential impact within niche environments has been reported through metagenomic analysis. This scientific expansion has been used to understand diseases and biome shifts in various patient types but has not been observed in COPD. With the ability to uncover the presence of a phage virome in COPD lungs via metagenomics, a foundational framework could be built for later use in diagnosing patients. The added discovery and characterization of lytic phages against clinical bacterial isolates could then also expand the therapeutic applications available, and aid in patient condition and stability.This study expands the current collection of bacterial strains found within COPD lungs. This library was utilized in the isolation of five novel phages against known COPD strains, including Stenotrophomonas maltophilia and Enterobacter cloacae. Metagenomic analysis of sputum provided by various lung types resulted in the discovery of thousands of vOTUs, eight of which were determined as complete genomes and putative phages. The diversity, presence and abundance of these vOTUs is both comparable and contrastable between lung types, along with a core set of shared vOTUs in all lung types. All together this has built a framework for future phage microbiome lung analysis.