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Abstract
The circulating strains of Bordetella pertussis have demonstrated a dramatic decline in the expression of pertactin, an outer membrane protein, in the last few decades. Despite substantial interests in using pertactin as a vaccine antigen, surprisingly little is known about its role in the biology and pathogenesis of B. pertussis. This dissertation discusses work using B. bronchiseptica, a close evolutionary progenitor of B. pertussis that naturally infects mice, to examine the role of pertactin in the context of the natural processes of colonization, growth, spread within the respiratory tract, shedding and transmission between hosts. The results indicated that pertactin contributes to shedding and transmission of B. bronchiseptica. Furthermore, in an attempt to inspect possible reasons behind the loss of pertactin expression from clinical isolates, the dissertation discusses three aspects of pertactin that distinguish it from other vaccine antigens, which may, individually or collectively, explain why only this antigen is being precipitously eliminated. Work on elucidating the functional properties of pertactin in B. bronchiseptica is complemented by our previous studies on the evolutionary origins of B. bronchiseptica that demonstrate its ability to survive inside amoeba and utilize it as a transmission vector. Here, we aimed to test whether the machinery which allows interactions with predatory amoeba is conserved in some or all Bordetella species. The results show that only some Bordetella species retain the ability to successfully interact with amoebae. Complete genomes for all 9 species allowed a Genome Wide Association Study (GWAS) approach that identified a set of genes that are associated with Bordetella-amoebal interactions. The final section of this dissertation describes work conducted on a pertussis-toxin-like factor in B. pseudohinzii identified via genome comparison between this bacterium and its closely related species. While recent studies have shown that B. pseudohinzii colonizes middle ears and persists for an extended time period, this dissertation describes how this ability may be linked to the production of these pertussis toxin-like proteins. Through these studies, we have gained a better understanding of the effects of various virulence factors on pathogenesis, transmission, and interactions with an amoebic transmission vector of Bordetella spp.