Genetically modified Salmonella – A promising addition to anti-cancer therapy
A new study has demonstrated that genetically modified Salmonella can be used to kill cancer cells. It has been known for years that certain strains of bacteria, including Salmonella enterica, can kill cancer cells. Salmonella enterica Serovar Typhimurium has been shown to not only colonize solid tumors, but also to exhibit an intrinsic antitumor effect. The problem however, has been that the bacteria causes severe food poisoning and can lead to sepsis and death in humans. Researchers have long grappled to find the balance between allowing it to kill the cancer and be safe for the patient.
The lipopolysaccharide structure (LPS) found in the outer membrane of bacteria, is one of the major inducers of sepsis, a life-threatening infection. Hence, the new study focuses on modifying the LPS of the Salmonella strain to make the bug less toxic. With the help of genetic engineering researchers deleted 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. The only problem with this mutant strain was that although it was most effective in killing tumor cells on getting there, it was less able to colonize the tumors.
Researchers then added another genetic modification, an inducible arabinose promoter. This 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. Due to the very rapid growth and cell division that occurs when Salmonella enters a tumor, the transition from a benign, invasive Salmonella to the toxic type occurs very rapidly in the tumor. Salmonella grows very slowly in a normal cell dividing once or twice in a 24-hour period, whereas in a tumor, the bacteria divide every hour.
Dr.Roy Curtiss, University Professor of Microbiology and Director, Center for Infectious Diseases and Vaccinology and Center for Microbial Genetic Engineering, believes that 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 hopes that the investigational therapy would soon be used in conjunction with chemotherapy and radiation therapy, once it gets to human trials.
The study has been published in this week’s issue of mBio, an online American Society for Microbiology.
