Population Genomics And Evolution Of Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium ubiquitous in diverse environments and an opportunistic pathogen in humans. It is a leading cause of chronic lung infections in cystic fibrosis patients and of hospital-acquired pneumonia and sepsis. With a large flexible genome and abundant mobile genetic elements, P. aeruginosa exhibits high levels of antimicrobial resistance (AMR), making it a significant public health threat. Evolutionary processes such as homologous recombination, and horizontal gene transfer generate extensive genomic diversity in this species and facilitate the spread of resistance genes. In this dissertation, I investigate the genetic and evolutionary factors shaping P. aeruginosa population structure and evolutionary dynamics. Using hundreds of publicly available genomes, I analyze patterns of homologous recombination and accessory gene content (Chapter 2), genome-wide associations between genetic variants and infection source (Chapter 3), and the distribution of mobile genetic elements and anti-phage defense systems (Chapter 4). Chapter 1 reveals two major phylogenetic lineages with distinct recombination patterns and unique accessory genome networks. Chapter 2 identifies genetic loci (SNPs, unitigs and accessory genes) differentiating isolates from cystic fibrosis lungs versus bloodstream infections, reflecting niche-specific adaptation. Chapter 3 shows that mobile genetic elements (plasmids, prophages, and insertion sequences) frequently co-occur with AMR genes and anti-phage defense systems in the same genomes, facilitating their spread. Together, these findings provide novel insights into the evolutionary dynamics that facilitate the emergence of epidemic strain clones, and antibiotic resistance, in P. aeruginosa, which can guide efforts in tracking outbreaks, infection control, and public health preparedness