Salmonella investigated as part of cancer therapy
Researchers have known for years certain strains of bacteria, including Salmonella enterica, can kill cancer cells.
Salmonella enterica Serovar Typhimurium has been shown to colonize solid tumors and show an intrinsic antitumor effect.
However, to use Salmonella, researchers must find a balance between allowing it to kill the cancer and be safe for the patient. The bacteria is commonly known for causing food poisoning.
Every year, Salmonella is estimated to cause one million illnesses in the US, with 19,000 hospitalizations and 380 deaths, according to the Centers for Disease Control and Prevention (CDC).
Use of genetically engineered microbes
Roy Curtiss, III, University Professor of Microbiology and Director, Center for Infectious Diseases and Vaccinology and Center for Microbial Genetic Engineering, the Biodesign Institute, Arizona State University, said there has long been interest in using genetically engineered microbes to target and destroy cells within solid tumours.
“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.”
Researchers modified the lipopolysaccharide structure (LPS) of the Salmonella strain to make it less toxic. LPS, found in the outer membrane of bacteria, is one of the major inducers of sepsis.
They 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.
Kill cancer cells and unable to cause disease
The team identified a particular mutant strain effective at killing cancer cells and shrinking tumours, and also unable to cause disease.
However, it was less able to colonize the tumours, although being most effective in killing tumour cells when getting there.
To address this problem, another genetic modification was added, an inducible arabinose promoter.
Modification allowed Salmonella to be injected in the mouse so it would not harm normal, healthy cells, was effective at colonizing 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 (time wise) in the tumour due to the very rapid growth and cell division that occurs when Salmonella enters a tumour," said Dr Curtiss.
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.
Source: mBio, an American Society for Microbiology journal
Online DOI: 10.1128/mBio.00254-15
“Efficiency of conditionally attenuated Salmonella enterica serovar Typhimurium in bacterium-mediated tumor therapy”
Authors: Frahm M, Felgner S, Kocijancic D, Rohde M, Hensel M, Curtiss R, III, Erhardt M, Weiss S
