title: Transcriptome of Proteus mirabilis in the murine urinary tract: virulence and nitrogen assimilation gene expression.
abstract: The enteric bacterium Proteus mirabilis is a common cause of complicated urinary tract infections. In this study, microarrays were used to analyze P. mirabilis gene expression in vivo from experimentally infected mice. Urine was collected at 1, 3, and 7 days postinfection, and RNA was isolated from bacteria in the urine for transcriptional analysis. Across nine microarrays, 471 genes were upregulated and 82 were downregulated in vivo compared to in vitro broth culture. Genes upregulated in vivo encoded mannose-resistant Proteus-like (MR/P) fimbriae, urease, iron uptake systems, amino acid and peptide transporters, pyruvate metabolism enzymes, and a portion of the tricarboxylic acid (TCA) cycle enzymes. Flagella were downregulated. Ammonia assimilation gene glnA (glutamine synthetase) was repressed in vivo, while gdhA (glutamate dehydrogenase) was upregulated in vivo. Contrary to our expectations, ammonia availability due to urease activity in P. mirabilis did not drive this gene expression. A gdhA mutant was growth deficient in minimal medium with citrate as the sole carbon source, and loss of gdhA resulted in a significant fitness defect in the mouse model of urinary tract infection. Unlike Escherichia coli, which represses gdhA and upregulates glnA in vivo and cannot utilize citrate, the data suggest that P. mirabilis uses glutamate dehydrogenase to monitor carbon-nitrogen balance, and this ability contributes to the pathogenic potential of P. mirabilis in the urinary tract.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Pearson
authors.forename: Alejandra
authors.initials: A
authors.lastname: Yep
authors.forename: Sara N
authors.initials: SN
authors.lastname: Smith
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D000641:Ammonia; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005969:Glutamate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D009584:Nitrogen / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011512:Proteus Infections / Q000382:microbiology*; D011513:Proteus mirabilis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014551:Urinary Tract / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D000641:Ammonia; D005969:Glutamate Dehydrogenase; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen