Many bacteria cause disease by invading cells and creating a safe niche in which to replicate. Cells respond to the infection by activating the immune system, and a chief challenge for bacteria is to avoid immune detection. Prior research had shown that bacteria inside the cytosol (the cell's expansive gel-like compartment) could be detected, but how bacteria within the cytosol are recognized has not been clear.
In the new work, Dr. John Brumell and colleagues at The Hospital for Sick Children studied the fate of Salmonella bacteria within the cytosol. These bacteria normally occupy vacuoles in host cells, but under some conditions they leave the vacuole and enter the cytosol. In this foreign environment, the bacteria were recognized by the ubiquitin system, a protein machine that applies molecular tags to cellular proteins to target them for destruction by the proteasome, essentially a molecular shredding device inside mammalian cells. These findings suggest that bacterial proteins are being destroyed by the proteasome within the cytosol during infection, and that this may play a key role in activation of the immune system. A surprising result came when Salmonella was compared with Listeria, a bacterium which normally occupies the cytosol. Listeria avoided recognition by the ubiquitin system by moving within this compartment. This suggests that Listeria and other bacteria that can colonize the cytosol do so in a manner that prevents activation of the immune system.