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Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract

Vancomycin‐resistant Enterococcus (VRE) poses a serious threat in hospitals where they densely colonize the intestinal tracts of patients. In vulnerable hosts, these pathogens may translocate to the bloodstream and become lethal. The ability to selectively reduce VRE in the intestinal tracts of pati...

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Autores principales: Geldart, Kathryn G., Kommineni, Sushma, Forbes, Madeline, Hayward, Michael, Dunny, Gary M., Salzman, Nita H., Kaznessis, Yiannis N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195901/
https://www.ncbi.nlm.nih.gov/pubmed/30377660
http://dx.doi.org/10.1002/btm2.10107
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author Geldart, Kathryn G.
Kommineni, Sushma
Forbes, Madeline
Hayward, Michael
Dunny, Gary M.
Salzman, Nita H.
Kaznessis, Yiannis N.
author_facet Geldart, Kathryn G.
Kommineni, Sushma
Forbes, Madeline
Hayward, Michael
Dunny, Gary M.
Salzman, Nita H.
Kaznessis, Yiannis N.
author_sort Geldart, Kathryn G.
collection PubMed
description Vancomycin‐resistant Enterococcus (VRE) poses a serious threat in hospitals where they densely colonize the intestinal tracts of patients. In vulnerable hosts, these pathogens may translocate to the bloodstream and become lethal. The ability to selectively reduce VRE in the intestinal tracts of patients could potentially prevent many of these translocation events and reduce the spread of the pathogen. Herein, we have engineered Escherichia. coli Nissle 1917 to produce and secrete three antimicrobial peptides, Enterocin A, Enterocin B, and Hiracin JM79, to specifically target and kill Enterococcus. These peptides exhibited potent activity against both Enterococcus faecium and Enterococcus faecalis, the two most prominent species responsible for VRE infections. We first discuss the optimization of the system used to express and secrete the peptides. We then show that by simultaneously expressing these peptides, both E. faecium and E. faecalis were drastically inhibited. We then demonstrate a suppression of the development of resistance when supernatant from the E. coli producer strains was used to treat E. faecium. Finally, we tested the efficacy of the probiotic in a VRE colonization model in mice. These studies showed that administration of the engineered probiotic significantly reduced the levels of both E. faecium and E. faecalis in the feces of male Balb/cJ mice.
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spelling pubmed-61959012018-10-30 Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract Geldart, Kathryn G. Kommineni, Sushma Forbes, Madeline Hayward, Michael Dunny, Gary M. Salzman, Nita H. Kaznessis, Yiannis N. Bioeng Transl Med Research Reports Vancomycin‐resistant Enterococcus (VRE) poses a serious threat in hospitals where they densely colonize the intestinal tracts of patients. In vulnerable hosts, these pathogens may translocate to the bloodstream and become lethal. The ability to selectively reduce VRE in the intestinal tracts of patients could potentially prevent many of these translocation events and reduce the spread of the pathogen. Herein, we have engineered Escherichia. coli Nissle 1917 to produce and secrete three antimicrobial peptides, Enterocin A, Enterocin B, and Hiracin JM79, to specifically target and kill Enterococcus. These peptides exhibited potent activity against both Enterococcus faecium and Enterococcus faecalis, the two most prominent species responsible for VRE infections. We first discuss the optimization of the system used to express and secrete the peptides. We then show that by simultaneously expressing these peptides, both E. faecium and E. faecalis were drastically inhibited. We then demonstrate a suppression of the development of resistance when supernatant from the E. coli producer strains was used to treat E. faecium. Finally, we tested the efficacy of the probiotic in a VRE colonization model in mice. These studies showed that administration of the engineered probiotic significantly reduced the levels of both E. faecium and E. faecalis in the feces of male Balb/cJ mice. John Wiley & Sons, Inc. 2018-09-08 /pmc/articles/PMC6195901/ /pubmed/30377660 http://dx.doi.org/10.1002/btm2.10107 Text en © 2018 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Reports
Geldart, Kathryn G.
Kommineni, Sushma
Forbes, Madeline
Hayward, Michael
Dunny, Gary M.
Salzman, Nita H.
Kaznessis, Yiannis N.
Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title_full Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title_fullStr Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title_full_unstemmed Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title_short Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract
title_sort engineered e. coli nissle 1917 for the reduction of vancomycin‐resistant enterococcus in the intestinal tract
topic Research Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195901/
https://www.ncbi.nlm.nih.gov/pubmed/30377660
http://dx.doi.org/10.1002/btm2.10107
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