Switch that enables Salmonella to sabotage host cells
16 April 2010
In humans, Salmonella causes diseases ranging from gastroenteritis to typhoid fever. It also causes similar diseases in livestock.
Before Salmonella can establish an infection, the bacterium must first sabotage a larger human or animal cell host cell where it can replicate. It does this by injecting a cocktail of 'virulence' proteins into the host cell, which interfere with the cell's defences and help the bacteria to grow.
The new findings, published today in the journal 'Science', reveal that a molecular switch needs to be triggered before the bacterial cell can inject its virulence proteins into a host cell.
When Salmonella attaches to a host cell to infect, it first assembles a needle-like structure on its surface ready to deliver the virulence proteins. Another set of bacterial proteins pass through the needle and poke a hole in the membrane of the host cell, creating a bridge between the bacterial cell and the host. During this time, the switch inside the bacterial cell acts like a safety catch, holding the virulence proteins back so they are not delivered prematurely.
Once the hole is created, the bacterial cell recognises the acidity of the host cell and this switches off the safety catch. The virulence proteins can then be delivered through the hole in order to commandeer the host cell.
The lead author of the study, Professor David Holden from the Department of Medicine at Imperial College London, explained: "The way in which a Salmonella cell delivers its virulence proteins to a host cell is a bit like the way in which a parked aeroplane delivers its passengers to a terminal building. After the plane taxis to its stand at the terminal, a loading bridge is used to connect the plane to the building. Similarly, the bacterial cell waits until it has assembled a special bridge before it delivers its passengers - the virulence proteins - to the host cell.
"On a plane there's a safety catch to prevent the doors opening before the bridge is ready, to stop the passengers falling out onto the tarmac. Similarly, the bacterial cell holds back delivery of its proteins using a molecular safety catch, until it senses that the pore has been assembled. Then the safety catch switches off, and virulence proteins can be delivered in an orderly manner. This process is crucial for Salmonella, because if it cannot deliver these proteins properly it cannot establish an infection," he added.
The researchers stress that the research is currently at an early stage but they hope that ultimately, it might be possible to use their findings to design better drugs or vaccines to combat Salmonella-related diseases.
The research was also supported by the Medical Research Council.
Image: Electron microscopy of Salmonella. Credit: Wellcome Images
Reference
Holden D et al. pH sensing by intracellular salmonella induces effector translocation. Science 2010 [Epub ahead of print].
