Depletion of intestinal phosphate after operative injury activates the virulence of P aeruginosa causing lethal gut-derived sepsis

Surgery. 2008 Aug;144(2):189-97. doi: 10.1016/j.surg.2008.03.045.


Background: We explored the possibility that the opportunistic pathogen, Pseudomonas aeruginosa senses low phosphate (Pi) as a signal of host injury and shifts to a lethal phenotype.

Methods: Virulence expression in P aeruginosa was examined in vitro under low phosphate conditions by assessing expression of the PA-I lectin, a barrier dysregulating protein, pyocyanin, and biofilm production, and PstS, a phosphate scavenging protein. Virulence expression in vivo was assessed using operatively injured mice (30% hepatectomy) intestinally inoculated with P aeruginosa.

Results: In vitro experiments demonstrated that acute phosphate depletion resulted in an increase (P = .001) in the expression the PA-I lectin, biofilm, pyocyanin, and PstS. Operative injury caused a depletion (P = .006) of intestinal phosphate concentration and increased mortality (60%) owing to intestinal P aeruginosa, which was prevented completely with oral phosphate supplementation and restoration of intestinal phosphate, neither of which were observed with systemic (IV) administration. PstS gene expression was 32-fold higher in P aeruginosa recovered from the cecum after hepatectomy indicating inadequate intestinal Pi.

Conclusions: Operative injury-induced intestinal phosphate depletion shifts the phenotype of P aeruginosa to express enhanced virulence in vitro and lethality in vivo. Intestinal phosphate repletion may be a novel strategy to contain pathogens associated with lethal gut-derived sepsis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adhesins, Bacterial / metabolism
  • Animals
  • Hepatectomy
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Lectins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Opportunistic Infections / etiology
  • Opportunistic Infections / metabolism
  • Opportunistic Infections / microbiology
  • Phosphate-Binding Proteins / metabolism
  • Phosphates / metabolism*
  • Phosphates / pharmacology
  • Pseudomonas Infections / metabolism*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / pathogenicity*
  • Pyocyanine / metabolism
  • Sepsis / etiology
  • Sepsis / microbiology*
  • Surgical Procedures, Operative / adverse effects*
  • Virulence


  • Adhesins, Bacterial
  • Lectins
  • Phosphate-Binding Proteins
  • Phosphates
  • adhesin, Pseudomonas
  • Pyocyanine