Man-made bacteria explode to fight cancer

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Nature

US scientists have used synthetic biology to create a man-made bacteria that will produce cancer drugs and then self-destruct and release the drugs at the site of tumors. The researchers synchronised the bacteria to release bursts of known cancer drugs when they self-destruct within the tumor environment. They say this approach is exciting because bacteria can grow within the inner regions of a tumour where conventional chemotherapy doesn’t always reach. The researchers found that treating mice with a combination of both the engineered bacteria and chemotherapy leads to reduction in cancer activity and extended survival compared to either therapy on its own.

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University of California, United States
  • Health / Medical
  • Society / Lifestyle
Last updated: Thu 3 Nov 2016

Media Release

From: Springer Nature

Synthetic biology: Bacteria as undercover therapeutic agents in mice (N&V) *IMAGES AND VIDEO*

Bacteria can be engineered to release anti-cancer drugs in synchronized cycles in mouse models of cancer, finds a paper published online in Nature this week. The system also allows bacterial populations to be controlled through periodic lysis (cell disintegration) of the bacterial colony.

There is growing interest in engineering bacteria to be used as living therapeutics, but responses in host organisms and long-term effectiveness of such systems need to be further evaluated.

Jeff Hasty and colleagues use a synthetic biology approach to engineer a genetic circuit — clusters of genes that impact each other’s expression — that controls the release of drugs in a tumour-targeting bacterium of the Salmonella strain. In this circuit, periodic synchronized cell lyses maximize the efficacy of delivery of the drugs. The authors first track bacterial population dynamics in colorectal tumours in mice. Subsequently, they orally administer the bacterium strain, alone or in combination with a clinical chemotherapeutic, to a mouse model of colorectal cancer. The authors find that the combination of both circuit-engineered bacteria and chemotherapy leads to reduction in cancer activity and extended survival compared to either therapy on its own.

The authors propose that their approach may help to leverage the tools of synthetic biology in order to exploit the propensity of certain bacteria to colonize sites in the body affected by disease. However, further work is needed before bacteria can be used as effective anti-cancer therapeutics. “Despite these features, bacteria alone (whether engineered or not), are unlikely to eradicate tumours”, explains Shibin Zhou in an associated News & Views article.

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 Video Springer Nature he video shows a colony of bacteria undergoing oscillations of synchronized lysis via timelapse fluorescence microscopy. The bacteria are carrying a plasmid-based gene circuit that activates lysis at a high cell population density via a quorum sensing molecule. The quorum sensing molecule acts as a positive feedback element in the circuit since it induces its own production and the production of the lysis gene. The colony grows until the sensing molecule reaches a critical density which causes synchronized transcription of the lysis protein across the entire population of bacteria. A green fluorescent protein is also produced to visualize the moment this synchronization occurs. A number of bacteria survive the synchronized lysis event and re-populate the colony until the next quorum threshold is reached, resulting in oscillatory population dynamics. Credit: Jeff Hasty, UC San Diego Web page 03 Nov 2016 6:42pm
 Video Springer Nature The video shows a colony of bacteria undergoing oscillations of synchronized lysis via timelapse fluorescence microscopy. The bacteria are carrying a plasmid-based gene circuit that activates lysis at a high cell population density via a quorum sensing molecule. The quorum sensing molecule acts as a positive feedback element in the circuit since it induces its own production and the production of the lysis gene. The colony grows until the sensing molecule reaches a critical density which causes synchronized transcription of the lysis protein across the entire population of bacteria. A green fluorescent protein is also produced to visualize the moment this synchronization occurs. A number of bacteria survive the synchronized lysis event and re-populate the colony until the next quorum threshold is reached, resulting in oscillatory population dynamics. Credit: Jeff Hasty, UC San Diego Web page 03 Nov 2016 6:49pm
 Video Springer Nature The video shows a colony of bacteria undergoing oscillations of synchronized lysis via timelapse fluorescence microscopy. The bacteria are carrying a plasmid-based gene circuit that activates lysis at a high cell population density via a quorum sensing molecule. The quorum sensing molecule acts as a positive feedback element in the circuit since it induces its own production and the production of the lysis gene. The colony grows until the sensing molecule reaches a critical density which causes synchronized transcription of the lysis protein across the entire population of bacteria. A green fluorescent protein is also produced to visualize the moment this synchronization occurs. A number of bacteria survive the synchronized lysis event and re-populate the colony until the next quorum threshold is reached, resulting in oscillatory population dynamics. Credit: Jeff Hasty, UC San Diego Web page 03 Nov 2016 6:35pm
 Research Springer Nature Please link to the article in online versions of your report (the URL will go live after the embargo ends) Web page 03 Nov 2016 7:40pm