Sorting out the steps in Salmonella infection
Salmonella bacteria invade the gut by piercing a needle-like structure through the intestinal lining to inject their own proteins into cells. First the needle complex moves into place, and then, in sequence, proteins called translocases and effectors infiltrate the host cell.
In a report published online February 3 in Science, a team led by Jorge E. Galán, D.V.M., Ph.D., the Lucille P. Markey Professor of Microbial Pathogenesis, analyzed the molecular choreography underlying this step-by-step process.
They found that a protein known as SpaO prepares the bacterium for attack by forming a large complex that includes components of the needle and translocases, but few effectors. However, mutant bacteria that lacked translocases showed high levels of effectors in the SpaO complex, indicating that the complex acts as a sorting platform, queuing up translocases and effectors to deliver them sequentially.
Galán says that understanding such mechanisms could lead to new therapies that do not kill microbes but prevent them from doing harm, an approach that could thwart the development of drug resistance in pathogens.