SciDev.Net

Five Shigella bacteria entering a gut cell

Philippe Sansonetti

The bacterium that causes dysentery uses a 'sword and shield' approach to attacks cells while protecting itself from the inflammation it triggers. The findings were published by Nicholas West and colleagues in Science this week.

Until now, how the bacterium, known as Shigella, is able to infect cells while protecting itself from the inflammation that it triggers has remained a mystery.

The researchers — led by Christoph Tang of Imperial College London, in the United Kingdom, and Philippe Sansonetti of the Pasteur Institute in France — found that Shigella protects itself using a shield of proteins that prevents the host's immune defences from destroying it.

The results are important because Shigella bacteria, which cause more than one million deaths each year, mostly in developing countries, are increasingly showing signs of resistance to several existing drugs.

Shigella infects the cells of the gut by pushing a 'molecular needle' into their membranes and injecting them with proteins. Once inside the cells, these proteins cause an inflammation.

Shigella's protective shield surrounds the molecular needle — seemingly preventing it from reaching its target gut cells. Tang's team showed, however, that Shigella is able to change the shape of the shield allowing the needle to stick out beyond it.

This allows Shigella to attack gut cells without compromising its protection.

Developing drugs and vaccines to target Shigella's shield could be difficult, as drug designers have never targeted the molecule it is made from before.

However, Sansonetti believes the findings do open the way for future treatments for dysentery and even vaccines against Shigella.

"This molecule has not been targeted in current therapies and vaccines but they offer the potential for interventions in the future," says Tang.

Link to full research paper by West et al in Science

Link to accompanying commentary by Normark et al in Science

Reference: Science 307, 1313 (2005)