Novel de novo synthesized phosphate carrier compound ABA‐PEG20k‐Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model.
Published: 16th April 2018
Authors: M. Wiegerinck, S. K. Hyoju, J. Mao, A. Zaborin, C. Adriaansens, E. Salzman et al.
Previous work has demonstrated that anastomotic leak can be caused by collagenolytic bacteria such as Enterococcus faecalis via an effect on wound collagen. In humans, E. faecalis is the organism cultured most commonly from a leaking anastomosis, and is not routinely eliminated by standard oral or intravenous antibiotics. Novel strategies are needed to contain the virulence of this pathogen when present on anastomotic tissues.
Polyphosphorylated polymer ABA‐PEG20k‐Pi20 was tested in mice for its ability to prevent anastomotic leak caused by collagenolytic E. faecalis. The study design included a distal colonic resection and anastomosis followed by introduction of E. faecalis to anastomotic tissues via enema. Mice were assigned randomly to receive either ABA‐PEG20‐Pi20 or its unphosphorylated precursor ABA‐PEG20k in their drinking water. The development of anastomotic leak was determined after the animals had been killed.
Overnight incubation of two different E. faecalis collagenolytic strains with 2 mmol/l of ABA‐PEG20k‐Pi20 led to near complete inhibition of collagenase production (from 21 000 to 1000 and from 68 000 to 5000 units; P < 0·001; 6 samples per group) without suppressing bacterial growth. In mice drinking 1 per cent ABA‐PEG20k‐Pi20, the phosphate concentration in the distal colonic mucosa increased twofold and leak rates decreased from eight of 15 to three of 15 animals (P < 0·001). In mice drinking ABA‐PEG20k‐Pi20, the percentage of collagenolytic colonies among E. faecalis populations present at anastomotic tissue sites was decreased by 6–4800‐fold (P = 0·008; 5 animals).
These data indicate that oral intake of ABA‐PEG20k‐Pi20 may be an effective agent to contain the virulence of E. faecalis and may prevent anastomotic leak caused by this organism. Read more