Scientists Use Flies to Discover How Anthrax Toxins Kill

Biology professors Ethan Bier and Annabel Guichard have injected fruit flies with anthrax to discover how the bacteria’s toxins flow through the bloodstream to become deadly.

According to Guichard, there are two active toxins in anthrax: the lethal factor (LF) and the edema factor (EF). These toxins cause blood vessels to become very leaky.

“The toxins both inhibit the cellular machine, called the exocyst, which acts like a postal truck to deliver materials such as adhesion molecules, as well as signaling molecules to points of cell-cell contact,” Bier said. “The two toxins work on different parts of that delivery truck but together they greatly reduce its ability to deliver the ‘goods.’”

As a result, the heart tries to pump harder and harder to pump fluid through the leaky blood vessels, but eventually the blood pressure drops to zero, causing death by toxic shock.

While the effects of these toxins were well known, researchers wanted to learn how the toxins worked together to create this result, and find out how to fight infections due to anthrax bacteria.

Guichard and Bier applied both toxins to fruit fly embryos and larvae. To isolate the two toxins, they got DNA from the anthrax bacteria that code for the two toxins, and inserted these genes into the fly genome.  They generated strains of flies that could make either EF or LF and then crossed them together to obtain flies that could make both toxins at the same time.

They observed that the LF toxin disrupts the wound-healing process. It inactivates the molecular system by interfering in the formation of the outer covering, resulting in holes in the chest cavities that eventually led to death. The EF toxin had a similar effect, blocking the cellular activity that creates wings.

The EF toxin prevents a signal that activates the notch pathway (a signaling system required to form the edge of the wing) from reaching the cell surface.

Bier compared the effects of these toxins on fruit fly wings to a mail delivery system. The toxins are inhibitors that prevent the mail truck (proteins, or the molecular system) from delivering to two different places in the cell. If both places do not receive their “letters,” they will not function properly. EF and LF both have to be present to create the leaky blood vessel effect. However, according to Bier, EF “seems to be far more important than LF for this effect.”

Dr. Victor Nizet at the UCSD School of Medicine also found that what happens to the flies infected by anthrax also happens to the cells lining blood vessels. Scientists there “identified the cell types and conditions for showing that anthrax toxins also blocked the function of the exocyst delivery system in human cells and mice,” Bier said.

Blood vessels become more leaky if their lining cells are torn apart by the LF and EF toxins. This shows that anthrax toxins attack two components in the molecules that join cells together, which in turn can cause the blood vessels to fall apart and lead to anthrax’s fatal consequences.

This study was published in the Oct. 14 edition of the journal Nature.

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