Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.
The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery.



We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth.



Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration.



PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa.



Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.
University of Chicago, Department of Surgery, Chicago, IL.
Sanjiv K
SK
Hyoju
Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands.
Robin E
RE
Klabbers
Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands.
Melissa
M
Aaron
University of Chicago, Department of Surgery, Chicago, IL.
Monika A
MA
Krezalek
University of Chicago, Department of Surgery, Chicago, IL.
Alexander
A
Zaborin
Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands.
Mara
M
Wiegerinck
University of Chicago, Department of Surgery, Chicago, IL.
Neil H
NH
Hyman
University of Chicago, Department of Surgery, Chicago, IL.
Olga
O
Zaborina
Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands.
Harry
H
Van Goor
University of Chicago, Department of Surgery, Chicago, IL.
John C
JC
Alverdy
D000284:Administration, Oral; D057868:Anastomotic Leak / Q000382:microbiology* / Q000517:prevention & control*; D000818:Animals; D018441:Biofilms / Q000187:drug effects; D017364:Collagenases / Q000096:biosynthesis*; D013505:Digestive System Surgical Procedures; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011122:Polyphosphates / Q000008:administration & dosage*; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000472:pathogenicity*; D012706:Serratia marcescens / Q000201:enzymology / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects*
D011122:Polyphosphates; D017364:Collagenases