A Promising Anti-Cancer Therapy: Genetically Altered Salmonella

For years, it has been observed that certain strains of bacteria have the capacity to eliminate cancer cells, one of such strains being Salmonella enterica. Now a new study conducted by the American Society for Microbiology has revealed how genetically altered Salmonella or, more specifically – Salmonella enterica Serovar Typhimurium – could one day be used as an effective form of cancer therapy. The research report features in this week's edition of the internet-based open access journal, mBio.

Not only has Salmonella enterica Serovar Typhimurium been known to colonize solid tumors, but the strain also shows an innate anti-tumor quality. However, Salmonella isn't exactly renowned for any health-aiding properties. For humans, the bacteria is one of the leading causes of food poisoning, it can result in septicaemia and, in some cases, even death. So before applying Salmonella in humans as any sort of treatment, researchers must first modify the bacteria, ensuring that it is safe to use without removing its anti-tumor effects.

The genetic engineering process involved eliminating the gene required in the composition of lipopolysaccharide (LPS) – one of the major causes of a life-threatening infection known as septicemia. The LPS structure is situated in the outer membrane of bacteria, and its removal makes the Salmonella bug far less hazardous. After testing several genetically altered strains of the bug on tumor bearing mice and human cancer cells, the researchers pin-pointed an individual strain that proved most effective at shrinking tumors and eradicating cancer cells. This particular strain was also incapable of causing disease.

“There has long been an interest in using genetically engineered microbes to target and destroy cells within solid tumors.” relayed Dr. Roy Curtiss III, PhD, a university professor of microbiology and researcher involved in the project. “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.”

However, though the identified mutant strain was the most effective at destroying tumor cells when applied, its showed a lesser capability of colonizing the tumors. To address this issue, another modification was added – a conclusive arabinose promoter. This final modification resulted in the Salmonella being much more effective at colonizing tumors by ensuring the bug only turned toxic after it entered the cancer cells.

“This transition from a benign, invasive Salmonella that doesn't hurt normal cells to the toxic type occurs very rapidly in the tumor due to the very rapid growth and cell division that occurs when Salmonella enters a tumor.” Dr. Curtiss explains. The Salmonella divide very rapidly in a tumor - once every hour as opposed to once or twice every 24 hours in normal cells.

According to the researchers, this form of therapy would best be utilized in tandem with chemo and radiation therapy once it enters the human trial phase.


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