Depletion of intestinal phosphate after operative injury activates the virulence of P aeruginosa causing lethal gut-derived sepsis.
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.
Long
Jason
J
Department of Surgery, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
Zaborina
Olga
O
Holbrook
Christopher
C
Zaborin
Alexander
A
Alverdy
John
J
D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D006498:Hepatectomy; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009894:Opportunistic Infections / Q000209:etiology / Q000378:metabolism / Q000382:microbiology; D028044:Phosphate-Binding Proteins / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D011710:Pyocyanine / Q000378:metabolism; D018805:Sepsis / Q000209:etiology / Q000382:microbiology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D014774:Virulence
D018829:Adhesins, Bacterial; D037102:Lectins; D028044:Phosphate-Binding Proteins; D010710:Phosphates; C038692:adhesin, Pseudomonas; D011710:Pyocyanine