Genomic Approach to Vaccine Design for Proteus mirabilis

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DESCRIPTION (provided by applicant): Urinary tract infections are one of the most common bacterial infections in the U.S. Proteus mirabilis is a major cause of infection in individuals with complicated urinary tracts. This member of the Enterobacteriaceae is notorious for its ability to cause urinary stone formation. Although several virulence factors have been identified in P. mirabilis, the recent completion of the sequencing of this genome has the potential to greatly increase our understanding of P. mirabilis pathogenesis. The first Specific Aim of this study is to determine the transcriptome of P. mirabilis in vitro and in vivo through use of a microarray. This aim will make use of the P. mirabilis genome to elucidate which genes are most highly expressed or most upregulated when this pathogen is grown in the mouse urinary tract. In the second Specific Aim, a mutant of a surface-expressed protein identified as upregulated in vivo by microarray analysis will be constructed. This mutant will be assessed in vivo for virulence in the murine model of UTI. The final Specific Aim will test the vaccinogenic potential of this protein. Completion of these aims may lead to the discovery of a useful component for a P. mirabilis vaccine.