Switch that enables Salmonella to sabotage host cells revealed in new study

New finding could ultimately lead to drugs that interfere with the switch in order to combat <em>Salmonella</em> and possibly other bacterial infections <em> - News Release</em>

Imperial College London News Release

Under strict embargo for
14.00 Eastern Time / 19.00 London Time
Thursday 15 April 2010

A new switch that enables Salmonella bacteria to sabotage host cells is revealed in a study published today in the journal Science.

The researchers behind the study, from Imperial College London, say that the new finding could ultimately lead to drugs that interfere with the switch in order to combat Salmonella and possibly other bacterial infections.

In humans, Salmonella causes diseases ranging from gastroenteritis to typhoid fever. It also causes similar diseases in livestock.

Before the Salmonella cell can replicate inside a much larger human or animal cell and establish an infection, it must first sabotage the cell by injecting it with a cocktail of 'virulence' proteins. These proteins interfere with the cell's defences and help the bacteria to grow.

The new research reveals that a switch needs to be triggered before the bacterial cell can inject its virulence proteins into a host cell.

First, the bacterial cell assembles a needle-like structure on its surface, to deliver the virulence proteins. Then, 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.

Salmonella (green) delivering its virulence proteins (red) inside a human cell

Once the hole is created, the bacterial cell recognises the pH of the host cell and this switches off the safety catch. This then allows the virulence proteins to be delivered through the hole into 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," added Professor Holden, whose work was supported by grants from the MRC and the Wellcome Trust.

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.

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Imperial College London
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Notes to editors:

1. "pH Sensing by Intracellular Salmonella Induces Effector Translocation" Science Express, Thursday 15 April 2010

Corresponding author: Professor David Holden, Imperial College London (for full list of authors please see paper)

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