NOVEL STRATEGIES TO DEVELOP BETTER BRUCELLOSIS VACCINES USING BRUCELLA ABORTUS RB51 AND B. NEOTOMAE
Date of Award
Doctor of Philosophy (PhD)
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Committee Member 2
Committee Member 3
The genus Brucella consists of Gram-negative, facultative intracellular coccobacilli that can cause chronic infections in several mammals. Brucella spp. can exhibit a smooth or rough phenotype; smooth Brucella spp. contain a surface-exposed O-polysaccharide in their cell wall structure while the rough Brucella spp. are devoid of the O-polysaccharide. Acquired immunity against Brucella infection is primarily cell-mediated and involves both CD4+ T cells and CD8+ T cell responses. However, antibodies to the O-polysaccharide also play a role in enhancing the protection against infections by virulent Brucella species in some hosts. B. abortus strain RB51 is a stable rough attenuated mutant which is used as a licensed live vaccine for bovine brucellosis in the United States and several other countries. Previous studies have shown that the wboA gene, which encodes a glycosyltransferase required for the synthesis of O-polysaccharide in Brucella, is disrupted in B. abortus RB51 by an IS711 element. Although low-levels of intra-cytoplasmic O-polysaccharide were produced when RB51 was complemented with a functional wboA gene (strain RB51WboA), it did not result in a smooth phenotype. This suggests that mutations in several genes of the O-polysaccharide biosynthesis pathway contribute to the rough phenotype of RB51. However, nucleotide sequence analysis has revealed that there are no other gene-disrupting mutations that could affect the smooth LPS synthesis in strain RB51.
Dabral, Neha, "NOVEL STRATEGIES TO DEVELOP BETTER BRUCELLOSIS VACCINES USING BRUCELLA ABORTUS RB51 AND B. NEOTOMAE" (2014). Open Access Dissertations. 1071.