Researchers at the University of Waterloo have developed engineered bacteria designed to invade and eat solid tumors from the inside out. The approach uses microbes that thrive in oxygen-free environments, targeting the low-oxygen cores of tumors. A genetic modification allows the bacteria to survive near oxygenated edges, controlled by a quorum-sensing mechanism.
Scientists at the University of Waterloo are advancing a novel cancer treatment by engineering bacteria to target and consume solid tumors internally. The strategy centers on Clostridium sporogenes, a soil bacterium that survives only in oxygen-free conditions. The inner cores of many solid tumors consist of dead cells and lack oxygen, providing an ideal habitat for these microbes to multiply and feed on nutrients.
"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. "So, we are now colonizing that central space, and the bacterium is essentially ridding the body of the tumor."
A key challenge arises as the bacteria spread outward toward the tumor's edges, where trace oxygen causes them to die before fully eradicating the cancer. To overcome this, the team inserted a gene from a related, oxygen-tolerant bacterium, enabling survival in low-oxygen areas. However, early activation of this trait could allow growth in oxygen-rich body parts like the bloodstream, posing risks.
The researchers addressed this by incorporating quorum sensing, a bacterial communication system using chemical signals. As bacterial numbers increase within the tumor, the signal strengthens, activating the oxygen-tolerance gene only when sufficient microbes are present. This ensures targeted action inside the tumor.
In prior work, the team genetically modified Clostridium sporogenes for better oxygen resistance. A subsequent experiment tested the quorum-sensing circuit by programming bacteria to produce green fluorescent protein, verifying activation timing. "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. "Each piece has its job. When assembled correctly, they form a system that works in a predictable way."
The project originated from PhD student Bahram Zargar's research under supervisors Ingalls and retired professor Dr. Pu Chen. It involves collaboration with CREM Co Labs in Toronto, co-founded by Zargar, and former doctoral student Dr. Sara Sadr. Future steps include integrating both modifications into one bacterium for pre-clinical tumor trials.
The findings appear in ACS Synthetic Biology (2025; 14(12): 4857).
