Enhancing the tropism of bacteria via genetically programmed biosensors.

Tiffany Chien, Tetsuhiro Harimoto, Benjamin Kepecs, Kelsey Gray, Courtney Coker, Nicholas Hou, Kelly Pu, Tamjeed Azad, Andoni Nolasco, Martina Pavlicova, Tal Danino

Nature biomedical engineering 2022 Jan

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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. © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Tiffany Chien, Tetsuhiro Harimoto, Benjamin Kepecs, Kelsey Gray, Courtney Coker, Nicholas Hou, Kelly Pu, Tamjeed Azad, Andoni Nolasco, Martina Pavlicova, Tal Danino. Enhancing the tropism of bacteria via genetically programmed biosensors. Nature biomedical engineering. 2022 Jan;6(1):94-104