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.

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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