Enhancing the tropism of bacteria via genetically programmed biosensors
| Autor: | Kelsey Gray, Nicholas Hou, Courtney Coker, Andoni Nolasco, Tal Danino, Kelly Pu, Tetsuhiro Harimoto, Martina Pavlicova, Benjamin Kepecs, Tamjeed Azad, Tiffany Chien |
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| Rok vydání: | 2019 |
| Předmět: |
biology
Preferential growth Bacteria Chemistry Biomedical Engineering Medicine (miscellaneous) Bioengineering Biosensing Techniques Bacterial growth biology.organism_classification Tropism Article Computer Science Applications Cell biology Oxygen Mice In vivo Sense (molecular biology) Animals Lactic Acid Gene Biosensor Biotechnology |
| Zdroj: | Nat Biomed Eng |
| ISSN: | 2157-846X |
| Popis: | Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Here we show that the tropism of engineered bacteria can be enhanced by coupling bacterial growth with genetic circuits that sense oxygen, pH or lactate through the control of the expression of essential genes. Bacteria that were engineered with pH or oxygen sensors showed preferential growth in physiologically relevant acidic or oxygen conditions, and reduced growth outside the permissive environments when orally delivered to mice. In syngeneic mice bearing subcutaneous tumours, bacteria engineered with both hypoxia and lactate biosensors coupled through an AND gate showed increased tumour specificity. The multiplexing of genetic circuits may be more broadly applicable for enhancing the localization of bacteria to specified niches. The tropism of engineered bacteria in vivo can be enhanced by genetic circuits, linked by AND-gate logic, that couple bacterial sensing and growth. |
| Databáze: | OpenAIRE |
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