Researchers at the University of Waterloo in Canada have reprogrammed a naturally occurring soil bacterium to infiltrate the heart of a tumour before attacking it, in an advance that could lead to a new class of highly targeted cancer therapies.
The work, reported by SciTechDaily and detailed in ACS Synthetic Biology, uses clostridium sporogenes to exploit the oxygen-starved cores of solid tumours. The engineered bacteria can burrow into cancers and destroy them from the inside out.
How the engineered bacteria work
Clostridium sporogenes is an obligate anaerobe, meaning it can grow only where there is no oxygen. That makes the dead-cell-rich, oxygen-poor cores of many tumours an ideal place for it to thrive. As the microbes spread towards a tumour's better-oxygenated edges, they typically perish, limiting their ability to clear the cancer completely.
To overcome that, the team introduced a gene from a related bacterium that allows greater tolerance to low oxygen levels. They also built a biological 'on switch' so the bacteria start eating only when needed inside the tumour, not in healthy, oxygen-rich tissues such as the bloodstream.
Expert insight and next steps
Dr Marc Aucoin, a chemical engineering professor at Waterloo, said: "Bacteria spores enter the tumour, 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. So, we are now colonising that central space, and the bacterium is essentially ridding the body of the tumour."
Dr Brian Ingalls, a professor of applied mathematics at Waterloo, said: "Using synthetic biology, we built something like an electrical circuit, but instead of wires we used pieces of DNA. Each piece has its job. When assembled correctly, they form a system that works in a predictable way."
In studies, the researchers showed they could make clostridium sporogenes more tolerant of oxygen. In a follow-up experiment, they engineered the bacteria to produce a green fluorescent protein only when the 'crowd' signal reached the right level - a visual stand-in for the therapeutic gene they ultimately plan to deploy.
Next, the team aims to combine both elements - oxygen tolerance and quorum-controlled activation - in a single bacterial strain and test it in preclinical tumour models. If successful, the approach could complement surgery, radiotherapy and chemotherapy by targeting the hard-to-reach, low-oxygen pockets that often allow cancers to persist or return.
