Engineered Bacteria Show Promise in Eating Away Cancer Tumors

In a groundbreaking approach to cancer treatment, scientists at the University of Waterloo are engineering bacteria to actively consume tumors from the inside out. This innovative strategy leverages microbes that thrive in oxygen-deprived environments – a common characteristic of solid tumor cores – to target and dismantle cancerous growths.

How it Works: Targeting the Tumor Microenvironment

The research centers around Clostridium sporogenes, a bacterium naturally found in soil and uniquely adapted to survive in the absence of oxygen. Solid tumors often develop an inner core of dead cells lacking oxygen, creating an ideal breeding ground for this microbe. “Bacteria spores enter the tumor, finding an environment where there are lots of nutrients and no oxygen, which this organism prefers, and so it starts eating those nutrients and growing in size,” explained Dr. Marc Aucoin, a chemical engineering professor at Waterloo ¹. “So, we are now colonizing that central space, and the bacterium is essentially ridding the body of the tumor.”

Overcoming the Oxygen Barrier: A Genetic Solution

A significant challenge in this approach lies in the fact that as the bacteria expand outward towards the tumor’s edges, they encounter oxygen, which is lethal to Clostridium sporogenes. To overcome this, researchers have genetically modified the bacteria to enhance their oxygen tolerance. They introduced a gene from a related bacterium, allowing the engineered microbes to survive longer in areas with low oxygen levels.

Controlled Activation: Quorum Sensing for Safety

To prevent premature activation of the oxygen-tolerance gene – which could lead to bacterial growth in oxygen-rich areas like the bloodstream – the team employed a sophisticated control mechanism called quorum sensing. This natural bacterial communication process relies on chemical signals. As the bacterial population grows within the tumor, the signal strength increases. Only when a sufficient number of bacteria are present does the signal trigger the activation of the oxygen-resistant gene, ensuring it functions only where and when it’s needed ².

Synthetic Biology and DNA Circuits

The team utilized principles of synthetic biology, constructing a system akin to an electrical circuit using DNA. “Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA,” said Dr. Brian Ingalls, a professor of applied mathematics at Waterloo ². “Each piece has its job. When assembled correctly, they form a system that works in a predictable way.” Prior research demonstrated the feasibility of genetically altering Clostridium sporogenes to withstand oxygen, and subsequent experiments confirmed the precise timing of the quorum sensing system using a green fluorescent protein marker.

Next Steps: Pre-Clinical Trials and Collaboration

The next phase of research involves combining the oxygen-tolerance gene and the quorum-sensing control system into a single bacterium and evaluating its effectiveness in pre-clinical trials against tumors. This research is a collaborative effort, involving the University of Waterloo and the Center for Research on Environmental Microbiology (CREM Co Labs) in Toronto ². The project similarly benefits from the contributions of Dr. Sara Sadr, a former Waterloo doctoral student.

Potential Implications and Future Outlook

This innovative approach represents a significant step forward in cancer therapy, offering a potentially new way to destroy tumors by harnessing the power of engineered bacteria. While still in the early stages of development, the research holds promise for a more targeted and effective cancer treatment in the future.