OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: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.
Authors: Baddr A Shakhsheer; Luke A Versten; James N Luo; Jennifer R Defazio; Robin Klabbers; Scott Christley; Alexander Zaborin; Kristina L Guyton; Monika Krezalek; Daniel P Smith; Nadim J Ajami; Joseph F Petrosino; Irma D Fleming; Natalia Belogortseva; Olga Zaborina; John C Alverdy Journal: J Gastrointest Surg Date: 2016-08-16 Impact factor: 3.452
Authors: Alexander Zaborin; Svetlana Gerdes; Christopher Holbrook; Donald C Liu; Olga Y Zaborina; John C Alverdy Journal: PLoS One Date: 2012-04-13 Impact factor: 3.240
Authors: Andrea D Olivas; Benjamin D Shogan; Vesta Valuckaite; Alexander Zaborin; Natalya Belogortseva; Mark Musch; Folker Meyer; William L Trimble; Gary An; Jack Gilbert; Olga Zaborina; John C Alverdy Journal: PLoS One Date: 2012-08-31 Impact factor: 3.240
Authors: Alexander Zaborin; Daniel Smith; Kevin Garfield; John Quensen; Baddr Shakhsheer; Matthew Kade; Matthew Tirrell; James Tiedje; Jack A Gilbert; Olga Zaborina; John C Alverdy Journal: mBio Date: 2014-09-23 Impact factor: 7.867
Authors: M Wiegerinck; S K Hyoju; J Mao; A Zaborin; C Adriaansens; E Salzman; N H Hyman; O Zaborina; H van Goor; J C Alverdy Journal: Br J Surg Date: 2018-04-16 Impact factor: 6.939
Authors: Marja B Pimentel; Fernando T P Borges; Fouad Teymour; Olga Y Zaborina; John C Alverdy; Kuili Fang; Seok Hoon Hong; Austeja Staneviciute; Yusheng J He; Georgia Papavasiliou Journal: J Mater Chem B Date: 2020-03-25 Impact factor: 6.331
Authors: Kristina L Guyton; Zoe C Levine; Ann C Lowry; Laura Lambert; Irena Gribovskaja-Rupp; Neil Hyman; Olga Zaborina; John Alverdy Journal: Dis Colon Rectum Date: 2019-08 Impact factor: 4.585
Authors: Richard A Jacobson; Kiedo Wienholts; Ashley J Williamson; Sara Gaines; Sanjiv Hyoju; Harry van Goor; Alexander Zaborin; Benjamin D Shogan; Olga Zaborina; John C Alverdy Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-10-11 Impact factor: 4.052
Authors: Sara Gaines; Sanjiv Hyoju; Ashley J Williamson; Jasper B van Praagh; Olga Zaborina; David T Rubin; John C Alverdy; Benjamin D Shogan; Neil Hyman Journal: J Gastrointest Surg Date: 2020-01-02 Impact factor: 3.452
Authors: Sara Gaines; Jasper B van Praagh; Ashley J Williamson; Richard A Jacobson; Sanjiv Hyoju; Alexander Zaborin; Jun Mao; Hyun Y Koo; Lindsay Alpert; Marc Bissonnette; Ralph Weichselbaum; Jack Gilbert; Eugene Chang; Neil Hyman; Olga Zaborina; Benjamin D Shogan; John C Alverdy Journal: Gastroenterology Date: 2019-10-23 Impact factor: 22.682