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

• Published in: Surgery Vol. 144; no. 2; pp. 189 - 197
• Main Authors: Long, Jason, MD, Zaborina, Olga, PhD, Holbrook, Christopher, MD, Zaborin, Alexander, PhD, Alverdy, John, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2008; Elsevier
• Subjects: Adhesins, Bacterial - metabolism; Animals; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; General aspects; Hepatectomy; Human bacterial diseases; Infectious diseases; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Lectins - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Opportunistic Infections - etiology; Opportunistic Infections - metabolism; Opportunistic Infections - microbiology; Phosphate-Binding Proteins - metabolism; Phosphates - metabolism; Phosphates - pharmacology; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - metabolism; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - metabolism; Pseudomonas Infections - microbiology; Pyocyanine - metabolism; Sepsis - etiology; Sepsis - microbiology; Surgery; Surgical Procedures, Operative - adverse effects; Virulence; Phosphates; Mortality; Virulence; Gut; Trauma; Bacteremia; Infection; Medicine; Sepsis syndrome; Depletion; Treatment; Surgery; Bacteriosis; Lesion
• ISSN: 0039-6060; 1532-7361
• 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.