Collagen degradation and MMP9 activation by Enterococcus faecalis contributes to intestinal anastomotic leak
| Autor: | Lynn E. Hancock, Jack A. Gilbert, Olga Zaborina, Mark Singer, Benjamin D. Shogan, Marc A. Ward, James N. Luo, Joseph P. Muldoon, Preston M. Luong, Alexander Zaborin, Simon Lax, Konstantin Umanskiy, Baddr A. Shakhsheer, Robin Klabbers, Natalia Belogortseva, Cindy Bethel, Gary An, John C. Alverdy, Vani J. Konda |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Peritonitis Anastomotic Leak MMP9 Enterococcus faecalis Article Microbiology Cell Line Pathogenesis Sepsis Mice Colon surgery Ischemia RNA Ribosomal 16S medicine Animals Humans Rats Wistar Intestinal Mucosa Caenorhabditis elegans Metalloproteinase biology business.industry Macrophages General Medicine medicine.disease biology.organism_classification Recombinant Proteins Anti-Bacterial Agents Rats Intestines Treatment Outcome Matrix Metalloproteinase 9 Collagenase Collagen business medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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