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Engineering Salmonella as intracellular factory for effective killing of tumour cells
Salmonella have many desirable properties as antitumour-agent due to its ability to proliferate inside tumours and induce tumour regression. Additionally, this bacterium can be genetically engineered to deliver therapeutic proteins intratumourally. The main limitation of this approach is the efficie...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964584/ https://www.ncbi.nlm.nih.gov/pubmed/27464652 http://dx.doi.org/10.1038/srep30591 |
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author | Camacho, Eva María Mesa-Pereira, Beatriz Medina, Carlos Flores, Amando Santero, Eduardo |
author_facet | Camacho, Eva María Mesa-Pereira, Beatriz Medina, Carlos Flores, Amando Santero, Eduardo |
author_sort | Camacho, Eva María |
collection | PubMed |
description | Salmonella have many desirable properties as antitumour-agent due to its ability to proliferate inside tumours and induce tumour regression. Additionally, this bacterium can be genetically engineered to deliver therapeutic proteins intratumourally. The main limitation of this approach is the efficient release of therapeutic molecules from intratumoural bacteria. Here we have developed an inducible autolysis system based in the lysis operon of the lambda phage that, in response to anhydrotetracycline, lysates Salmonella thus releasing its content. The system was combined with a salicylate cascade system that allows efficient production of therapeutic molecules in response to aspirin and with a sifA mutation that liberates bacteria from the vacuoles to a cytosolic location. The combination of these three elements makes this strain a putative powerful instrument in cancer treatment. We have used this engineered strain for the intracellular production and delivery of Cp53 peptide. The engineered strain is able to sequentially produce and release the cytotoxic peptide while proliferating inside tumour cells, thus inducing host cell death. Our results show that temporal separation of protein production from protein release is essential to efficiently kill tumour cells. The combined system is a further step in the engineering of more efficient bacteria for cancer therapy. |
format | Online Article Text |
id | pubmed-4964584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49645842016-08-08 Engineering Salmonella as intracellular factory for effective killing of tumour cells Camacho, Eva María Mesa-Pereira, Beatriz Medina, Carlos Flores, Amando Santero, Eduardo Sci Rep Article Salmonella have many desirable properties as antitumour-agent due to its ability to proliferate inside tumours and induce tumour regression. Additionally, this bacterium can be genetically engineered to deliver therapeutic proteins intratumourally. The main limitation of this approach is the efficient release of therapeutic molecules from intratumoural bacteria. Here we have developed an inducible autolysis system based in the lysis operon of the lambda phage that, in response to anhydrotetracycline, lysates Salmonella thus releasing its content. The system was combined with a salicylate cascade system that allows efficient production of therapeutic molecules in response to aspirin and with a sifA mutation that liberates bacteria from the vacuoles to a cytosolic location. The combination of these three elements makes this strain a putative powerful instrument in cancer treatment. We have used this engineered strain for the intracellular production and delivery of Cp53 peptide. The engineered strain is able to sequentially produce and release the cytotoxic peptide while proliferating inside tumour cells, thus inducing host cell death. Our results show that temporal separation of protein production from protein release is essential to efficiently kill tumour cells. The combined system is a further step in the engineering of more efficient bacteria for cancer therapy. Nature Publishing Group 2016-07-28 /pmc/articles/PMC4964584/ /pubmed/27464652 http://dx.doi.org/10.1038/srep30591 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Camacho, Eva María Mesa-Pereira, Beatriz Medina, Carlos Flores, Amando Santero, Eduardo Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title | Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title_full | Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title_fullStr | Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title_full_unstemmed | Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title_short | Engineering Salmonella as intracellular factory for effective killing of tumour cells |
title_sort | engineering salmonella as intracellular factory for effective killing of tumour cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964584/ https://www.ncbi.nlm.nih.gov/pubmed/27464652 http://dx.doi.org/10.1038/srep30591 |
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