Published online 20 August 2008 | Nature | doi:10.1038/news.2008.1056

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Suicidal Salmonella sacrifice themselves to allow their clones to get a foothold in the gut.

Bacteria can commit suicide to help their brethren establish more damaging infections — and scientists think that they can explain how this behaviour evolved.

Kamikaze bacteria can help their fellow colonists to thrive. MICHAEL ABBEY / SCIENCE PHOTO LIBRARY

The phenomenon, called self-destructive cooperation, can help bacteria such as Salmonella typhimurium and Clostridium difficile to establish a stronghold in the gut.

By studying mice infected with S. typhimurium, researchers from Switzerland and Canada have now demonstrated how this 'kamikaze' behaviour arose.

The team, led by Martin Ackermann of ETH Zurich in Switzerland, studied how S. typhimurium expresses the Type III secretion systems virulence factors (TTSS-1) that inflame the gut. This eradicates intestinal microflora that would otherwise compete for resources — but also kills most of the S. typhimurium cells in the vicinity. After this assault, the way is clear for remaining S. typhimurium to take advantage and further colonise the gut.

But in the middle of the gut cavity, or lumen, only about 15% of the S. typhimurium population actually expresses TTSS-1. In contrast, in the tissue of the gut wall, almost all bacteria express TTSS-1. As more bacteria invade the tissue, gut inflammation increases and kills off the invaders (especially those within the tissue) - along with the other competing gut flora.

"We thought it was a very strange phenomenon," says team member Wolf-Dietrich Hardt, also at ETH Zurich. "The bacteria in the gut lumen are genetically identical, but some of them are prepared to sacrifice themselves for the greater good. You could compare this act to Kamikaze fighter pilots of the Japanese army."

Kamikaze genes

This self-destructive cooperation relies on the genes controlling this suicidal behaviour not always being expressed. This 'phenotypic noise' means that only a fraction express TTSS-1, allowing the kamikaze genes to persist in the population. If every cell expressed the genes, they would all commit suicide, benefiting none of the population.

The team concluded that acts of self-destructive cooperation can arise, providing that the level of "public good" — in this case, the inflammation of the gut — is high enough. Crucially, cooperative individuals must also benefit from other cooperative acts more often than individuals who are not cooperating, a situation the scientists call 'assortment'.

In the case of gut bacteria, assortment can arise if the minimum number of pathogens required to infect a host is relatively small — as few as 100 cells, in cases such as Escherichia coli.

Change of strategy

The findings, published in Nature1, chime well with long-established theories on the evolution of altruism and co-operation.

If a gene for sibling altruism is always expressed, it will tend to disappear, because those members of a clutch or litter who possess it may sacrifice themselves for those who do not. However, if the gene is present but not always expressed, it can persist, because some of its carriers may survive to pass it on to subsequent generations.

The research could also aid the design of more potent strategies against pathogenic bacteria. The Salmonella bacterium causes one of the most common bacterial infections in western countries, and is highly dangerous among the elderly and frail. "There is no doubt that a vaccine for Salmonella in humans is needed," says Hardt. "And many strains infecting livestock are becoming resistant to antibiotics.

"But based on our results, I would suggest that the usual strategy of targeting the vaccine against a virulence factor might not be the best strategy, if only a small fraction of the bacteria express it."