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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI068324-02
Application #
7348339
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Korpela, Jukka K
Project Start
2007-02-01
Project End
2009-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
2
Fiscal Year
2008
Total Cost
$51,278
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Pearson, Melanie M; Yep, Alejandra; Smith, Sara N et al. (2011) Transcriptome of Proteus mirabilis in the murine urinary tract: virulence and nitrogen assimilation gene expression. Infect Immun 79:2619-31
Pearson, Melanie M; Rasko, David A; Smith, Sara N et al. (2010) Transcriptome of swarming Proteus mirabilis. Infect Immun 78:2834-45
Lane, M Chelsea; Li, Xin; Pearson, Melanie M et al. (2009) Oxygen-limiting conditions enrich for fimbriate cells of uropathogenic Proteus mirabilis and Escherichia coli. J Bacteriol 191:1382-92
Pearson, Melanie M; Mobley, Harry L T (2008) Repression of motility during fimbrial expression: identification of 14 mrpJ gene paralogues in Proteus mirabilis. Mol Microbiol 69:548-58
Pearson, Melanie M; Sebaihia, Mohammed; Churcher, Carol et al. (2008) Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol 190:4027-37