Bacteria are voracious eaters. They obtain nutrients by digesting dead organic matter and other materials, such as wood, and some can even degrade plastic and petroleum products. Now, researchers have turned their attention—and bacteria’s “hunger” —elsewhere. Soon, engineered bacteria will be a carefully guided bio-attack on tumors, offering a new therapy against cancer.
Scientists at the University of Waterloo are developing a new cancer treatment that consumes tumors from the inside, using engineered bacteria that naturally thrive in oxygen-free habitats. Because the cores of many solid tumors lack oxygen, programmed bacterial invasion can destroy those tumors.
“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,” said 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.”
The star of the therapy is Clostridium sporogenes, a strictly anaerobic bacterium (which survives only in the absence of oxygen) commonly found in soil. The interior of tumors is composed of dead cells and lacks oxygen, creating ideal conditions for this microbe to multiply, spread, and consume the tumor’s contents.
In an otherwise foolproof strategy, the challenge of keeping the microbial battalion active and running becomes a problem. As the bacteria expand outward and reach areas of the tumor exposed to some oxygen, they begin to fall like flies. To prevent this, the team inserted a gene from another bacterium, Staphylococcus aureus. The agr-QS system transferred from the latter allows the bacteria to survive in oxygenic conditions near the outer regions of the tumor.
A density-driven switch turns on oxygen tolerance. Activating the feature too early can allow bacteria to grow in oxygen-rich areas, such as the bloodstream, which can be unsafe. To prevent that, scientists used a natural bacterial communication process called quorum sensing.
As the bacterial population increases, bacteria release chemical signals that amplify manifold. After enough bacteria accumulate in a tumor does the signal become strong enough to switch on oxygen resistance. The timing ensures that their survival mechanism is triggered only in a specific window.
In an earlier study, the team showed that genetically altered Clostridium sporogenes can adapt to an oxygenic environment. In a follow-up experiment, they tested whether the quorum-sensing system activated at the intended time by programming cells to express a green fluorescent protein at that time.
An exciting feat of synthetic biology, the next step is to combine the oxygen-tolerance gene and the quorum-sensing control system into a single bacterium and to conduct pre-clinical trials to assess its efficacy and safety. The Waterloo team is collaborating with the Center for Research on Environmental Microbiology (CREM Co Labs), a Toronto company co-founded by Dr. Bahram Zargar, whose interdisciplinary health innovation work brought together experts from diverse fields of science.
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