Bordetella species: Sensing and Evading Host Immunity
Open Access
- Author:
- Hester, Sara E
- Graduate Program:
- Biochemistry, Microbiology, and Molecular Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 09, 2012
- Committee Members:
- Eric Thomas Harvill, Dissertation Advisor/Co-Advisor
Sarah Ellen Ades, Committee Member
Robert Paulson, Committee Member
Kathleen Postle, Committee Member
Andrew Fraser Read, Committee Member - Keywords:
- Bordetella species
Sensing the Environment
Immunomodulation
Horizontal Gene Transfer
Host Specificity
Bacterial Pathogen - Abstract:
- To evade host immunity and successfully colonize and persist within host, pathogens must sense and appropriately respond to the environment. This dissertation investigates several interactions between the host and the classical bordetellae, which must not only sense their environment, but evade host immunity to persist in the host. Little is known concerning what environmental cues the classical bordetellae sense within the host. Here, we investigated their response to growth in 5% CO2 conditions and identified increased transcription of several known virulence factor genes. Additionally, transcription of two genes, cyaA and fhaB, was found to be increased in 5% CO2 conditions in the absence of a functional BvgS—the master virulence factor gene regulator. These data indicate that there are additional virulence factor gene regulatory mechanisms that respond to growth in 5% CO2 conditions. On the other hand to evade host innate immune response, Bordetella species secrete a molecule(s) that inhibits LPS-induced IL-1 secretion in murine macrophages. B. bronchiseptica and B. pertussis have additional mechanisms to induce secretion of IL-1, but B. parapertussis does not. This inhibitory molecule did not affect transcription or downstream inflammasome products, such as caspase-1, suggesting that it blocks release of IL-1 from macrophages. Furthermore, additional host immune factors are important for the control of Bordetella species colonization in the respiratory tract, such as complement. B. parapertussisov strains, isolated only from sheep, are rapidly cleared from the lower respiratory tract of mice, unlike the other classical bordetellae. B. parapertussisov strains did not produce an O-antigen, were susceptible to murine complement deposition and killing, and colonized complement deficient mice more efficiently. Unlike mouse serum, sheep serum did not efficiently kill B. parapertussisov strains, indicating a role for complement in host adaptation of this species. Evasion of cross-protective immune responses through antigenic variation is one strategy employed by pathogens to evade recognition by the immune response. The Bordetella species produce antigenically distinct O-antigens that appear, based on SNP density and phylogenetic analysis, to have been horizontally transferred, specifically the genes thought to be responsible for serotype differences. Additionally, poorly immunogenic O-antigens do not appear to generate cross-protective immune responses, suggesting that O-antigen variation allows for evasion of protective immune responses. Combined, the data herein suggest CO2 sensing by the classical bordetellae, the subversion of IL-1 secretion, a role for complement in host adaptation of a Bordetella species, and horizontal transfer of O-antigen serotype-specific genes to evade protective immunity. Finally, this thesis also discusses implications of this research and future directions resulting directly from it.