Identification of Secondary Mutations Which Enhance and Stabilize the Attenuation of Brucella HTRA Mutants: Improving Brucella HTRA-Based Strains as Vaccine
Annual rept. 1 Aug 98-31 Jul 99
LOUISIANA STATE UNIV MEDICAL CENTER SHREVEPORT
Pagination or Media Count:
Genetic and biochemical studies indicate that the bacterial stress response protease HtrA represents an important defense against oxidative damage. More importantly, many facultative intracellular pathogens rely upon the HtrA to help them resist killing by the oxidative killing pathways of host macrophages. Studies completed to date under this contract indicate that although the Brucella HtrA contributes to resistance to oxidative killing in vitro and resistance to killing by cultured murine neutrophils and macrophages, Brucella HtrA mutants are not attenuated in the murine host. Attempts to combine htrA mutations with other mutations predicted to attenuate the brucellae have also met with limited success. During the course of these studies, however, we have identified five other genetic loci, hfq, bacA, katE, clpA and uvrA, which offer considerable promise as targets for the construction of novel Brucella vaccine candidates. We plan to continue investigating the nature of the attenuation of the corresponding Brucella mutants as well as examining the potential of these mutants to elicit protective immunity in the mouse model.
- Genetic Engineering and Molecular Biology