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Updated: Jul 8, 2026

Establishment and Characterization of UTI and CAUTI in a Mouse Model
Published on: June 23, 2015
The high-affinity phosphate transporter Pst is a virulence factor for Proteus mirabilis during complicated urinary
Sandra M Jacobsen1, Mary C Lane, Jean M Harro
1Department of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA.
Abstract:
Proteus mirabilis is a ubiquitous bacterium associated with complicated urinary tract infection (UTI). Mutagenesis studies of the wild-type strain HI4320 in the CBA mouse model of ascending UTIs have identified attenuated mutants with transposon insertions in genes encoding the high-affinity phosphate transporter Pst (pstS, pstA). The transcription of the pst operon (pstSCAB-phoU) and other members of the phosphate regulon of Escherichia coli, including alkaline phosphatase (AP), are regulated by the two-component regulatory system PhoBR and are repressed until times of phosphate starvation. This normal suppression was relieved in pstS::Tn5 and pstA::Tn5 mutants, which constitutively produced AP regardless of growth conditions. No significant growth defects were observed in vitro for the pst mutants during the independent culture or coculture studies in rich broth, phosphate-limiting minimal salts medium, or human urine. Mutants complemented with the complete pst operon repressed AP synthesis in vitro and colonized the mouse bladder in numbers comparable to the wild-type strain HI4320. Therefore, the Pst transport system imparts a significant in vivo advantage to wild-type P. mirabilis that is not required for in vitro growth. Thus, the Pst transporter has satisfied molecular Koch's postulates as a virulence factor in the pathogenesis of urinary tract infection caused by P. mirabilis.
Insights
The Pst transporter is crucial for Proteus mirabilis virulence in urinary tract infections (UTIs). This high-affinity phosphate transporter provides an in vivo advantage, though it is not essential for bacterial growth in vitro.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Proteus mirabilis is a common cause of complicated urinary tract infections (UTIs).
- Phosphate uptake is essential for bacterial survival and is tightly regulated.
- The high-affinity phosphate transporter (Pst) system and its regulation are key to bacterial adaptation.
Purpose of the Study:
- To investigate the role of the Pst transporter in the virulence of Proteus mirabilis during UTIs.
- To determine if the Pst system is essential for in vitro growth or provides an in vivo advantage.
Main Methods:
- Generated Pst transporter mutants (pstS, pstA) of Proteus mirabilis HI4320 using transposon mutagenesis.
- Assessed bacterial growth in vitro under various conditions (rich broth, minimal media, human urine) and in vivo using a CBA mouse model of ascending UTIs.
- Analyzed alkaline phosphatase (AP) production as an indicator of phosphate regulation.
Main Results:
- Mutants lacking functional Pst transporter constitutively produced alkaline phosphatase, indicating dysregulated phosphate homeostasis.
- Pst mutants showed no significant growth defects in vitro.
- Pst mutants exhibited reduced colonization in the mouse bladder compared to wild-type, but complementation restored colonization ability.
Conclusions:
- The Pst transport system confers a significant in vivo advantage to Proteus mirabilis during UTI pathogenesis.
- The Pst transporter acts as a virulence factor, satisfying molecular Koch's postulates.
- Targeting the Pst transporter could be a potential therapeutic strategy for P. mirabilis UTIs.
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