Genetically modified Salmonella — bacteria that causes severe food poisoning — can be used to kill cancer cells, a new study has claimed.
“There has long been interest in using genetically engineered microbes to target and destroy cells within solid tumours,” said Roy Curtiss, from the Arizona State University.
“I think this study goes a significant way in developing some strategies that will help in the overall means of using Salmonella as part of a cancer therapy,” he said.
For years, researchers have known that certain strains of bacteria, including Salmonella enterica, can kill cancer cells.
Specifically Salmonella enterica Serovar Typhimurium has been shown to not only colonise solid tumours, but also to exhibit an intrinsic anti-tumour effect.
However, in order to use Salmonella as a weapon against cancer in humans, researchers must find a balance between allowing it to kill the cancer and be safe for the patient.
The bacteria, commonly known for causing severe food poisoning, can lead to sepsis and death in humans.
In the study, the researchers focused on modifying the lipopolysaccharide structure (LPS) of the Salmonella strain to make the bug less toxic.
LPS, found in the outer membrane of bacteria, is one of the major inducers of sepsis, a life-threatening infection.
Researchers used genetic engineering to delete genes involved in the synthesis of the LPS, and then tested various modified Salmonella strains to see how they performed in test tube studies with human cancer cells and in tumour bearing mice.
They identified a particular mutant strain that was the most effective at killing cancer cells and shrinking tumours, and also unable to cause disease.
However, this mutant strain was less able to colonise the tumours, although being most effective in killing tumour cells when getting there.
To address this problem, the researchers then added another genetic modification, an inducible arabinose promoter.
The modification allowed the Salmonella to be injected in the mouse in a form that would not harm normal, healthy cells, was effective at colonising tumours, and after entering cancer cells, would turn toxic.
“This transition from a benign, invasive Salmonella that doesn’t hurt normal cells to the toxic type occurs very rapidly in the tumour due to the very rapid growth and cell division that occurs when Salmonella enters a tumour,” he said.
In a normal cell, Salmonella grows very slowly, dividing once or twice in a 24-hour period, but in a tumour, the bacteria divide every hour.
According to Curtiss, the investigational therapy would probably be used in conjunction with chemotherapy and radiation therapy, once it gets to human trials.
The study was published in mBio, an American Society for Microbiology journal.
