Environmentally Controlled Invasion of Cancer Cells by Engineered Bacteria
Bacteria can sense their environment, distinguish between cell types, and deliver proteins to eukaryotic cells. Here, we engineer the interaction between bacteria and cancer cells to depend on heterologous environmental signals. We have characterized invasin from Yersinia pseudotuburculosis as an ou...
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| Veröffentlicht in: | Journal of molecular biology 2006-01, Vol.355 (4), p.619-627 |
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| container_title | Journal of molecular biology |
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| creator | Anderson, J. Christopher Clarke, Elizabeth J. Arkin, Adam P. Voigt, Christopher A. |
| description | Bacteria can sense their environment, distinguish between cell types, and deliver proteins to eukaryotic cells. Here, we engineer the interaction between bacteria and cancer cells to depend on heterologous environmental signals. We have characterized invasin from
Yersinia pseudotuburculosis as an output module that enables
Escherichia coli to invade cancer-derived cells, including HeLa, HepG2, and U2OS lines. To environmentally restrict invasion, we placed this module under the control of heterologous sensors. With the
Vibrio fischeri lux quorum sensing circuit, the hypoxia-responsive
fdhF promoter, or the arabinose-inducible
araBAD promoter, the bacteria invade cells at densities greater than 10
8
bacteria/ml, after growth in an anaerobic growth chamber or in the presence of 0.02% arabinose, respectively. In the process, we developed a technique to tune the linkage between a sensor and output gene using ribosome binding site libraries and genetic selection. This approach could be used to engineer bacteria to sense the microenvironment of a tumor and respond by invading cancerous cells and releasing a cytotoxic agent. |
| doi_str_mv | 10.1016/j.jmb.2005.10.076 |
| format | Article |
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Yersinia pseudotuburculosis as an output module that enables
Escherichia coli to invade cancer-derived cells, including HeLa, HepG2, and U2OS lines. To environmentally restrict invasion, we placed this module under the control of heterologous sensors. With the
Vibrio fischeri lux quorum sensing circuit, the hypoxia-responsive
fdhF promoter, or the arabinose-inducible
araBAD promoter, the bacteria invade cells at densities greater than 10
8
bacteria/ml, after growth in an anaerobic growth chamber or in the presence of 0.02% arabinose, respectively. In the process, we developed a technique to tune the linkage between a sensor and output gene using ribosome binding site libraries and genetic selection. This approach could be used to engineer bacteria to sense the microenvironment of a tumor and respond by invading cancerous cells and releasing a cytotoxic agent.</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/j.jmb.2005.10.076</identifier><identifier>PMID: 16330045</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adhesins, Bacterial - genetics ; Adhesins, Bacterial - metabolism ; Aliivibrio fischeri - genetics ; Aliivibrio fischeri - metabolism ; Bacterial Proteins - genetics ; Base Sequence ; cancer ; Cell Count ; Cell Hypoxia - physiology ; Cell Line, Tumor ; Escherichia coli ; Escherichia coli - physiology ; Gene Expression Regulation ; Genetic Engineering ; Genetic Vectors - genetics ; Humans ; invasin ; lux ; Neoplasms - microbiology ; Neoplasms - pathology ; Neoplasms - therapy ; Promoter Regions, Genetic - genetics ; synthetic biology ; therapeutic bacteria ; Vibrio fischeri ; Yersinia ; Yersinia pseudotuberculosis - genetics ; Yersinia pseudotuberculosis - metabolism</subject><ispartof>Journal of molecular biology, 2006-01, Vol.355 (4), p.619-627</ispartof><rights>2005 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-46aaf4781fd47bc39950ff8522a7bd0cb69de904f2add4bb1c88b90f225be2d23</citedby><cites>FETCH-LOGICAL-c448t-46aaf4781fd47bc39950ff8522a7bd0cb69de904f2add4bb1c88b90f225be2d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jmb.2005.10.076$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16330045$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anderson, J. Christopher</creatorcontrib><creatorcontrib>Clarke, Elizabeth J.</creatorcontrib><creatorcontrib>Arkin, Adam P.</creatorcontrib><creatorcontrib>Voigt, Christopher A.</creatorcontrib><title>Environmentally Controlled Invasion of Cancer Cells by Engineered Bacteria</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>Bacteria can sense their environment, distinguish between cell types, and deliver proteins to eukaryotic cells. Here, we engineer the interaction between bacteria and cancer cells to depend on heterologous environmental signals. We have characterized invasin from
Yersinia pseudotuburculosis as an output module that enables
Escherichia coli to invade cancer-derived cells, including HeLa, HepG2, and U2OS lines. To environmentally restrict invasion, we placed this module under the control of heterologous sensors. With the
Vibrio fischeri lux quorum sensing circuit, the hypoxia-responsive
fdhF promoter, or the arabinose-inducible
araBAD promoter, the bacteria invade cells at densities greater than 10
8
bacteria/ml, after growth in an anaerobic growth chamber or in the presence of 0.02% arabinose, respectively. In the process, we developed a technique to tune the linkage between a sensor and output gene using ribosome binding site libraries and genetic selection. 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Yersinia pseudotuburculosis as an output module that enables
Escherichia coli to invade cancer-derived cells, including HeLa, HepG2, and U2OS lines. To environmentally restrict invasion, we placed this module under the control of heterologous sensors. With the
Vibrio fischeri lux quorum sensing circuit, the hypoxia-responsive
fdhF promoter, or the arabinose-inducible
araBAD promoter, the bacteria invade cells at densities greater than 10
8
bacteria/ml, after growth in an anaerobic growth chamber or in the presence of 0.02% arabinose, respectively. In the process, we developed a technique to tune the linkage between a sensor and output gene using ribosome binding site libraries and genetic selection. This approach could be used to engineer bacteria to sense the microenvironment of a tumor and respond by invading cancerous cells and releasing a cytotoxic agent.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>16330045</pmid><doi>10.1016/j.jmb.2005.10.076</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adhesins, Bacterial - genetics Adhesins, Bacterial - metabolism Aliivibrio fischeri - genetics Aliivibrio fischeri - metabolism Bacterial Proteins - genetics Base Sequence cancer Cell Count Cell Hypoxia - physiology Cell Line, Tumor Escherichia coli Escherichia coli - physiology Gene Expression Regulation Genetic Engineering Genetic Vectors - genetics Humans invasin lux Neoplasms - microbiology Neoplasms - pathology Neoplasms - therapy Promoter Regions, Genetic - genetics synthetic biology therapeutic bacteria Vibrio fischeri Yersinia Yersinia pseudotuberculosis - genetics Yersinia pseudotuberculosis - metabolism |
| title | Environmentally Controlled Invasion of Cancer Cells by Engineered Bacteria |
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