EXPLORING THE GLOBAL VIROME AND DECIPHERING THE ROLE OF PHAGES IN CYSTIC FIBROSIS

Viruses are the most abundant and diverse life form on Earth. In Chapter 1 of this dissertation, a global census of the number of viral particles showed that 6.03 x 1031 viral particles are distributed across almost every ecosystem. The global census results showed that most viruses are in soils and sediments, two unexplored biomes for viral diversity. Accurate and fast bioinformatics methods to explore viral and bacterial composition in metagenomic datasets are presented in Chapter 2 as “Fragment Recruitment Assembly Purification (FRAP). Phages are viruses that infect bacteria, their role in polymicrobial infections such as Cystic Fibrosis is explored. Cystic Fibrosis is a genetic disease in which the lung phenotype promoted mucus accumulation and microbial colonization. A multi-omics strategy to explore changes in the lung microbial community during acute pulmonary exacerbations is presented in Chapter 3 as the “Cystic Fibrosis Rapid Response: Translating Multi-omics data into Clinically Relevant Information”. In Chapter 4 eight acute exacerbations were studied and a trend of loss of diversity and viral lytic lifestyle was onserved. Two cystic fibrosis patients studied in Chapter 4 were colonized by antibiotic resistant bacteria from the genera Achromobacter. Both patients suffered fatal exacerbations. This motivated the isolation and characterization of lytic phages to be used as antimicrobials against bacterial infections. In Chapter 5 twelve Achromobacter phages are presented and their use as antimicrobials is proposed