Genetically Engineered Salmonella Promising As Anti-Cancer Therapy

Genetically Engineered Salmonella Promising As Anti-Cancer Therapy
Colonies of Salmonella enterica (serovar typhimurium)
(Credit: Wikipedia)
A new study has demonstrated that genetically modified Salmonella can be used to kill cancer cells. The study is published in the journal mBio.
 
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 colonize solid tumors, but also to exhibit an intrinsic antitumor 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 new 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. The 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 tumor bearing mice. They identified a particular mutant strain that was the most effective at killing cancer cells and shrinking tumors, and also unable to cause disease. However, this mutant strain was less able to colonize the tumors, although being most effective in killing tumor 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 colonizing tumors, and after entering cancer cells, would turn toxic.
 
According to the researchers, the investigational therapy would probably be used in conjunction with chemotherapy and radiation therapy, once it gets to human trials.
 
Based on material originally posted by American Society for Microbiology.