Salmonella bacteria cause several diseases – however, they have features that make them very interesting for cancer medicine: The germs migrate into tumours and lead to the death of aberrant cells. Scientists from the Helmholtz Centre for Infection Research (Helmholtz-Zentrum für Infektionsforschung) in Braunschweig, Germany, now discovered that Salmonella form communities within the tumour. They develop so-called biofilms as a reaction upon the attacks of the immune system. On the one hand, a biofilm protects the bacteria. On the other hand, it improves the therapeutic effect – a very useful side effect. The results have now been published in the latest issue of the scientific journal “Cellular Microbiology”.
For years, the HZI research group “Molecular Immunology” is investigating how Salmonella help to defeat tumours in mice. They already found out: Immune cells that recognize the bacteria send out a certain messenger substance. This makes the blood vessel within the cancerous tissue accessible for bacteria to enter the tumour. Since the blood vessels in the tumour are more permeable, blood accumulates within the cancerous tissue and a necrosis develops – the aberrant cells die off.
When the scientists took a deeper look onto how the bacteria are able to survive within the cancerous tissue and assist in destroying the tumour, they observed something that was previously unknown: The bacteria form a biofilm within the tumour.
A biofilm is a community of bacteria that live together within a protective slime layer. Biofilms can be found everywhere on almost all surfaces, some of them helping our body such as the bacterial communities in our gut or on our skin. They protect against infections. However, other biofilms are a threat for the body such as cavity causing bacterial communities on our teeth. Even more severe are the problems caused by biofilms within the lungs of patients suffering from cystic fibrosis. “Here, the bacteria can multiply in the tenacious mucus and are very well protected against antibiotics or the immune system,” says Dr. Siegfried Weiss, head of the HZI research group “Molecular Immunology”. Until now only few possibilities exist to study such unhealthy biofilms which is necessary to develop new therapies or drugs to fight them.
Dr. Katja Crull, scientist in Dr. Weiss’ research group examined how biofilm formation and tumour-fighting are connected. For this, she infected tumour-bearing mice with genetically modified Salmonella that are unable to form biofilms. Interestingly, without the bacterial community the colonization of the tumour and its destroying was severely deteriorated.
As biofilms help to protect against the immune system, the scientists then infected tumour-bearing mice that lack certain immune cells with normal, unmodified Salmonella. Also under these conditions the bacteria did not form biofilms within the tumour. “Thus, the Salmonella hide within the tumour from certain immune cells and are protected in their biofilm against the immune system,” says Dr. Katja Crull. What actually increases the danger of the bacteria leads to an improved fight against cancerous tissue. To purposefully use these features may one day enable innovative cancer therapies.
Dr. Siegfried Weiss emphasizes that tumours could furthermore now be a completely new model to investigate biofilm formation within tissues. “Such experiments are still a big challenge and only few models exist until now. Studies on biofilms in tumours may be a new approach to develop and test new drugs and therapies.”
Biofilm formation by Salmonella enterica serovar Typhimurium colonizing solid tumours. Crull K, Rohde M, Westphal K, Loessner H, Wolf K, Felipe-López A, Hensel M, Weiss S. Cell Microbiol. 2011 Aug; 13(8). doi: 10.1111/j.1462-5822.2011.01612.x.