Our principal goal is to analyze the role(s) that DNA repair and recombination functions play in relevant models of bacterial pathogenesis. In selected bacterial systems, DNA repair functions are known to contribute to pathogenesis. For example, repair-defective mutants of Salmonella were found to lose pathogenicity; and the loss of virulence was correlated with the inability of these mutants to survive the damage from the oxidative burst within the macrophage. A number of pathogens not only survive, but even flourish within professional phagocytes; these include some Brucelleae, Campylobactereae, Chlamydieae, Edwardsielleae, Listereae, Mycobacterieae and Yersineae. The function the repair mechanisms play in virulence of each of these pathogens is not yet understood. Our major emphasis will be to study DNA repair in certain representative bacteria with a focus Brucella abortus, which causes undulant fever in humans and abortions and infertility in cattle and other domestic animals. Little is understood about DNA repair in Brucella abortus; a better characterization of repair in these organisms will be required to determine its role(s) in virulence. We propose the following specific aims to address the question """"""""What are the roles of DNA repair and recombination in pathogenesis of specific intracellular bacteria?"""""""": 1) Isolation and molecular characterization of specific repair and recombination genes in Brucella abortus, 2) Characterize the SOS regulation of DNA repair genes in Brucella. 3.) Analysis of inhibition of the Brucella abortus repair networks by dominant defective recA mutants.
