RT Journal Article
SR Electronic
T1 Collagen degradation and MMP9 activation by <em>Enterococcus faecalis</em> contribute to intestinal anastomotic leak
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 286ra68
OP 286ra68
DO 10.1126/scitranslmed.3010658
VO 7
IS 286
A1 Shogan, Benjamin D.
A1 Belogortseva, Natalia
A1 Luong, Preston M.
A1 Zaborin, Alexander
A1 Lax, Simon
A1 Bethel, Cindy
A1 Ward, Marc
A1 Muldoon, Joseph P.
A1 Singer, Mark
A1 An, Gary
A1 Umanskiy, Konstantin
A1 Konda, Vani
A1 Shakhsheer, Baddr
A1 Luo, James
A1 Klabbers, Robin
A1 Hancock, Lynn E.
A1 Gilbert, Jack
A1 Zaborina, Olga
A1 Alverdy, John C.
YR 2015
UL http://stm.sciencemag.org/content/7/286/286ra68.abstract
AB Even under the most expert care, a properly constructed intestinal anastomosis can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis. The cause of anastomotic leak remains unknown, and its incidence has not changed in decades. We demonstrate that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of anastomotic leak through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were colonized by E. faecalis strains that showed an increased collagen-degrading activity and also an increased ability to activate host MMP9, both of which contributed to anastomotic leakage. We demonstrate that the E. faecalis genes gelE and sprE were required for E. faecalis–mediated MMP9 activation. Either elimination of E. faecalis strains through direct topical antibiotics applied to rat intestinal tissues or pharmacological suppression of intestinal MMP9 activation prevented anastomotic leak in rats. In contrast, the standard recommended intravenous antibiotics used in patients undergoing colorectal surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent leak in our rat model. Finally, we show in humans undergoing colon surgery and treated with the standard recommended intravenous antibiotics that their anastomotic tissues still contained E. faecalis and other bacterial strains with collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the intestinal tissue contributing to anastomotic leak.