Dissertation

Adaptation of Bordetella bronchiseptica to Survival Within the Mammalian Respiratory Tract

McKay, Liliana S

2024

Overview

To be effective pathogens, bacteria must adapt to the microenvironments they infect within a host. The respiratory tract can be broadly divided into two environments: the upper and lower respiratory tracts. The classical bordetellae, including Bordetella bronchiseptica, infect both the upper and lower respiratory tracts of their hosts and must therefore adjust their physiologies as they transition between these environments. This dissertation investigates three aspects of B. bronchiseptica adaptation to the respiratory tract. First, we investigated which genes are expressed specifically in the lower respiratory tract, focusing on one putative gene: BB1259. Our data indicate that BB1259 is not required for infection despite its putative expression pattern. Second, we biochemically characterized a two-component regulatory system, PlrSR, required for persistent infection in the lower respiratory tract. We found that PlrSR is a canonical two component system, with PlrS functioning as both a kinase and phosphatase to PlrR. We also showed that PlrS phosphatase activity, in addition to PlrS kinase activity, is required during infection. Third, we interrogated the role of cytochrome oxidases during infection, focusing on the evolutionary adaptation within the classical bordetellae towards life within the mammalian respiratory tract. No individual cytochrome oxidase was necessary during infection. However, the combination of the three cytochrome oxidases conserved between B. bronchiseptica and the closely related B. pertussis were sufficient for infection, with one cytochrome oxidase, CyoABCD1, being sufficient for infection in both mouse models tested. Understanding adaptation to the respiratory tract environment could lead to new therapeutic targets and thus address the public health risk still caused by the classical bordetellae despite widespread vaccination. In addition, researching how bacteria survive within the different environments of the respiratory tract also increases our knowledge of host physiology in areas that are difficult to assess directly like the surface of epithelial cells. Overall, this work contributes broadly to our understanding of the physiology of respiratory pathogens within the respiratory tract.

• Publisher: ProQuest Dissertations & Theses
• Subject: Immunology / Microbiology / Pathology / Public health
• ISBN: 9798346873419