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Are bacteria turning our own weapons against us?

May 20, 2004

Scientists have identified what may be a completely new way in which bacteria defend themselves against their hosts. The bacteria have stolen a key defensive gene from the very animals that they are invading - and are now using it against them. This research from the European Molecular Biology Laboratory (EMBL) is featured in today's issue of the open access journal Genome Biology.

EMBL Team Leader Toby Gibson points out that such a discovery has clear medical implications. "This study gives us insight into how infectious bacteria function - microbes that cause diseases such as pneumonia, whooping cough and plague are using our own gene against us," he explains. "With this new information, we could potentially produce antibodies to give our immune systems a way to identify the bacteria and block the activity of these weapons."

The gene in question makes a blood protein called alpha-2-macroglobulin, or a2M. This protein and its relatives have been studied in many different animals, and all have a similar function: defending the organism against attacking parasites.

TEPs are a2M-type proteins being studied in the mosquito by EMBL malaria researchers Stephanie Blandin and Elena Levashina. The mosquito is an interesting animal to study such defense proteins - its blood-sucking lifestyle brings along a steady stream of invaders.

"These a2M-type genes are a strong line of defense - they trap molecules that parasites use to attack our cells," notes Blandin. The malaria researchers wanted to learn more about the evolution of TEP, so they enlisted the help of the Gibson team, including PhD student Aidan Budd.

Their findings were completely unexpected.

"During a search for genes similar to TEPs, we were very surprised to discover a bacterial a2M gene - there are no previous reports of such a finding," says Budd.

EMBL Scientists predict that the a2M is used by a bacterium to protect itself from attacks against its cell wall by the host immune system. This bacterial defence is active only when the invader is being counter-attacked by the host.

"The way in which bacterial a2M functions makes it particularly attractive for a potential vaccination target," notes Budd. "Antibodies to the a2M could eliminate the microbe's a2M protection against the host - allowing the bacteria to succumb to the host's immune defenses."

Budd also noted that the gene didn't show a typical pattern for inheritance. In a normal case, he explained, if a gene is found in animals and bacteria - you would find this gene distributed throughout many other organisms like plants and yeasts.

But in the case of a2M, they only found the gene in two groups: in animals, and in bacteria which invade animals. The gene never seems to occur anywhere else.

"This suggested that bacteria have stolen it from multi-cellular organisms," Budd adds. "So a piece of the animal immune system - a weapon usually aimed against them - now seems to be helping bacteria invade our bodies."

On top of that, invading bacteria with the a2M gene belong to many different groups that are not at all closely related. "We can already see more than ten cases where the gene has gone from one bacteria to another one," notes Gibson. "This gene is being passed around like trading cards in a school playground."

European Molecular Biology Laboratory (EMBL)