Phylogenomic Variations and Host Adaptations of the Classical Bordetellae

Open Access
Author:
Park, Jihye
Graduate Program:
Integrative Biosciences
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
February 26, 2013
Committee Members:
  • Eric Thomas Harvill, Dissertation Advisor
  • Eric Thomas Harvill, Committee Chair
  • Ross Cameron Hardison, Committee Member
  • Webb Colby Miller, Committee Member
  • Kateryna Dmytrivna Makova, Committee Member
  • Edward G Dudley, Committee Member
Keywords:
  • Bordetella
  • Genomes
  • Host adaptation
  • Bacterial diversity
  • Horizontal gene transfer
  • Virulence
Abstract:
Understanding host adaptation, virulence phenotypes, and evasion of host immunity by different bacterial species and/or strains lays the groundwork for shedding light on the mechanisms behind bacterial diversity. It will also suggest approaches to prevent new emerging infectious diseases and to design better vaccines for both humans and animals. This dissertation investigates the genetic basis for bacterial diversity in virulence and host-pathogen interactions, using a unique set of subspecies referred to as the classical bordetellae. These lineages are very closely related but differ in host ranges and disease symptoms. Using comparative genomic and phylogenomic analysis, we studied seven newly sequenced genomes with four previously published genomes of the classical bordetellae (Chapter 2). We predicted the total genome (pan-genome) of the classical bordetellae, showing substantial diversity of genome content in these closely related pathogens. The diversity may contribute to their host specificities to different animals, including humans, and virulence phenotypes. We also discussed multiple evolutionary mechanisms, such as mutations, loss of genes, and horizontal gene transfer (HGT), which likely contribute to host adaptation and evasion of host immunity. Focusing on smaller gene clusters important for pathogenesis, we investigated the similarity and diversity of the Type I through Type VI secretion system loci (T1SS-T6SS) compared to other bacteria, as well as within the classical bordetellae (Chapter 3). In addition, we identified protein candidates that are functionally associated with these secretion systems without known orthologs in other bacteria. Understanding the functions of these proteins will likely help us comprehend the Bordetella-specific functions of these secretion systems in pathogenesis. It will also help us find target virulence factors as treatment possibilities. In addition, diversity of secretion systems in the classical bordetellae strains may contribute to host adaptation and virulence phenotypes, as each species uses unique sets of secretion systems. Different evolutionary mechanisms, such as mutation, recombination, and HGT, are driving the evolution of these virulence factor loci. Lastly, we not only predicted recombination–mediated HGT as the mechanism of classical bordetellae O-antigen diversity, but we also confirmed the biological selective advantage of these diverse O-antigen serotypes in in vitro and in vivo experiments (Chapter 4). This interdisciplinary analysis suggests that HGT has allowed for multiple Bordetella species/strains to circulate in host populations and to evade protective immunity against differing O-antigen-induced antibodies. In summary, this dissertation contributes to linking genomic differences, evolutionary mechanisms, and biological selective pressures that may contribute to the diversity of bacterial characteristics, such as host specificity, pathogenesis, and evasion of immunity. This work has important implications to the advancement of public health and agricultural sustainability, because our interdisciplinary analysis sheds light on bacterial speciation, diversity, and host adaptation, not only within the classical bordetellae but also in all pathogens.