Color-enhanced microscopy image showing Salmonella typhimurium (red) invading cultured human cells (yellow-green). Image credit: Rocky Mountain Laboratories, NIAID (CC0)
Salmonellae are a group of bacteria that can cause vomiting and diarrhea if we consume contaminated food. Once in the bowel, the bacteria get inside our cells, where they stay in a compartment called the vacuole. This environment is very acidic, and the inside of the microbes also becomes more acidic in response. This change helps Salmonella to switch on genes that allow them to survive and infect humans, but it is still unclear how this mechanism takes place.
To investigate this question, Liew, Foo et al. harnessed a recent technique called super-resolution imaging, which lets scientists see individual molecules in a cell. First, the technique was used to count a protein called SsrB as well as the enzyme that activates it, SsrA. The role of SsrB is to bind to DNA and turn on genes involved in making proteins that help Salmonella thrive. These studies revealed that the levels of SsrA/B proteins increased three-fold in an acidic environment.
Then, Liew, Foo et al. followed SsrB inside cells, knowing that fast-moving particles are free in solution, while slow-moving particles are typically bound to DNA. In acidic conditions, the proportion of SsrB bound to DNA doubled. Finally, further experiments revealed that when the environment was acidic, SsrB became five times more likely to bind to DNA. Taken together, the results suggest that acidic conditions trigger a cascade of events which switch on genetic information that allows Salmonella to survive.
If SsrB could be prevented from responding to acid stress, it could potentially stop Salmonella from surviving inside host cells. This knowledge should be applied to drive new treatment strategies for Salmonella and other microbes that infect human cells.
