Scientists hypothesize explanation for key step in anthrax infection process

U.S. researchers recently formed a new hypothesis about a key step in the anthrax infection process after exploring the behavior of anthrax toxins using an artificial membrane.

Researchers with the National Institute of Standards and Technology and the U.S. Army Medical Research Institute for Infectious Diseases found the anthrax bacteria may use a previously undiscovered mechanism to deliver protein molecules that poison victims. The findings could result in a more effective anthrax cure.

Anthrax bacteria kill individuals by releasing three toxins working together to destroy cells. One toxin, PA, attaches to the membrane of a cell and acts as a landing spot for the other toxins, LF and EF.

After several LF and EF molecules attach to the PA toxin, the cell membrane wraps the toxins in an endosome membrane bubble and tries to destroy the toxins. The cell tries to make the interior of the endosome bubble more acidic, but the LF and EF toxins escape from the endosome before that happens and attack the interior of the cell.

While the current hypothesis suggests the LF and EF completely unfold and squeeze through a narrow hole the PA forms in the endosomal membrane, the studies used to support the hypothesis only tested short segments of the toxins.

The researchers explored how full-length toxins behave using an artificial cell membrane. The team found the LF and EF toxins bonded to the PA, suggesting it would be difficult, if not impossible, for the LF and EF toxins to enter the cell through the narrow PA pore.

The team found it was the bound toxins that tend to rupture cell membranes. The researchers suggested that it was perhaps the complexes of EF or LF bound to PA toxins that enter cells and that the complexes are the active toxins inside cells.

While the new hypothesis could explain prior experimental results, John Kasianowicz, an NIST physical scientist, said the new hypothesis was not a certainty.

"We don't know enough to choose between these theories -- and in fact it's possible that the toxins escape the endosome by more than one mechanism," Kasianowicz said. "But it's important that we better understand this step in the process to thwart anthrax more effectively."