ucture. When SopE binds to these two factors, the cell changes its surface and Salmonellae can penetrate into the cell. Previously, the researchers had assumed that this cell invasion brought about by SopE causes the diarrhoea.
Unexpected immune response
However, Hardt and his research group have now shown that Cdc42 and Rac1 are also a part of the cell’s early warning system. This system is indispensable for a rapid, non-specific defence against disease pathogens. What the two molecules do is to activate, via a route that is still unknown, the molecule Caspase-1, which is a cornerstone of inflammatory responses in the cell and also becomes active in sunburn, for example. Caspase-1 in turn activates chemical messengers that attract phagocytes such as macrophages. These finally put an end to the Salmonellae that penetrated into the intestinal tissue. On the other hand, earlier observations suggest that the Salmonellae that remain in the intestinal lumen can benefit from the resulting inflammation.
The perfidiousness of SopE is that the bacteria tamper with, of all things, a communication system which a cell cannot simply replace or switch off, because otherwise the non-specific immune response would fail to happen or the cell’s skeleton would be paralysed. Consequently, it is also not easy to find an active ingredient that disables Caspase-1, for example, to prevent the infection. Hardt stresses “That would impair the host’s general fitness more severely than the infection by Salmonellae.”
Diarrhoea is the lesser evil
Animals in which Caspase-1 did not function would quickly perish in the wild. This was shown in experiments on mice that lacked Caspase-1. Salmonellae and other disease pathogens infect the internal organs of these animals more severely. Thus the host is in a dilemma: although Caspase-1 allows Salmonellae to cause diarrhoea – allow them to colonise the host’s intestinal lumen more easily – without this protein, an animal or human being would be highly vulnerable to a large number of disease pathogens. Consequently diarrhoea is the lesser of the two evils.
Ironically, not all strains of Salmonella possess SopE. Only certain strains that have incorporated the genetic code for SopE into their own genome from a bacteria-specific virus, a bacteriophage, and can express it, can produce this substance. However, SopE is only one of 12 candidate chemical messengers that Salmonellae use to “crack” their host’s cell. That’s why Hardt’s researchers are now also studying how the other virulence factors operate.
Müller AJ et al. The S. Typhimurium Effector SopE Induces Caspase-1 Activation in Stromal Cells to Initiate Gut Inflammation. Cell Host&Microbe. 2009 Aug 20; 6:(2) 125-36.