MOLECULAR EVOLUTION OF VIRULENCE AND ANTIGENIC DIVERSITY IN BORDETELLA BRONCHISEPTICA
Open Access
- Author:
- Buboltz, Anne M
- Graduate Program:
- Biochemistry, Microbiology, and Molecular Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 23, 2008
- Committee Members:
- Eric Thomas Harvill, Committee Chair/Co-Chair
Avery August, Committee Member
Peter John Hudson, Committee Member
Kenneth Charles Keiler, Committee Member
Kathleen Postle, Committee Member - Keywords:
- comparative genomics
Bordetella
bronchiseptica
phylogenetics
mlst - Abstract:
- Bordetella is a genus of Betaproteobacteria consisting of nine species, many of which cause respiratory disease. The population structure of Bordetella is clonal, as the majority of strains fall into a small number of genotypic complexes. While strains of B. bronchiseptica are very closely related genetically, this species exhibits a high level of phenotypic diversity. For example, B. bronchiseptica has been isolated from the respiratory tract of more than 20 species of mammals, causes a wide-variety of severities of respiratory disease, strains can differ up to 100,000-fold in their lethal doses and can differ in their expression of virulence factors. Despite this phenotypic diversity exhibited by B. bronchiseptica strains, very few studies have mapped these traits to a phylogenetic tree to examine the evolution of these traits. Beyond that, even fewer studies have determined the underlying genetics factors associated with the phenotypic trait that was mapped which makes it impossible to determine if the phenotypic diversity is associated with the same genetic factor and to examine the molecular evolution of this trait. Therefore, using a wide range of approaches including a murine model of infection, comparative genomics and transcriptomics, and phylogenetics, the molecular evolution of the genetics factors that appear to contribute to phenotypic diversity, measured either in terms of virulence or antigenic variation, were examined. The first section shows that the gene encoding adenylate cylcase toxin (CyaA) was replaced with a novel operon via lateral gene transfer (LGT) in a hypovirulent lineage of B. bronchiseptica. The next section shows that the type three secretion system (TTSS) contributes to the increased virulence of a B. bronchiseptica lineage. Finally, we found that two distinct O-Antigen loci, which appear to encode antigenically distinct O-Antigen serotypes, which homologously recombine between B. bronchiseptica lineages. Combined, data contained herein suggest that lateral gene transfer, differential gene expression and homologous recombination all contribute to the phenotypic diversity of B. bronchiseptica strains. We discuss the implication of these findings on both within and outside the Bordetella field, consider the ecological forces that may cause and maintain this diversity and future avenues of research that result from these works.