Date of Award

January 2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Comparative Pathobiology

First Advisor

Ramesh Vemulapalli

Committee Member 1

Harm HogenEsch

Committee Member 2

Carolyn Guptill-Yoran

Committee Member 3

Mohamed Seleem

Abstract

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.

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