Anthrax literally cuts the gas line. The toxin works like a pair of scissors, snipping off the ends of a key protein and preventing the transmission of messages within the cell. As a result, immune cells never receive the green light to assemble the actin motor, Southwick's findings demonstrate.
"Together, these studies provide important clues about how anthrax escapes the immune system during infection," said Nick Duesbery, Ph.D. deputy director for research operations and senior scientific investigator at the Van Andel Institute in Grand Rapids, Mich.
In 1998, Duesbery discovered that the toxin interrupts the transmission of signals within cells. But Dr. Southwick's study is the first to explain how anthrax can short-circuit a cell signal to block neutrophil movement, a realization that has eluded scientists for years. The finding almost escaped Southwick's research team as well, which was looking for proteins that interacted directly with the toxin.
"I would say it's the scientific equivalent of finding a needle in a haystack," Southwick said.
The team compared before and after snapshots of neutrophils exposed to a purified form of the toxin, as well as images showing how protein expression changed in cells. After scrutinizing the images for hours, During finally identified one protein that seemed to disappear upon exposure to anthrax. The protein turned out to be responsible for gathering the components of actin and shuttling them to the center of the cell, where they are assembled into filaments.
"We've discovered that through this pathway, lethal toxin blocks the function of a protein that regulates how actin assembles," said Southwick, who believes his findings may also explain how anthrax paralyzes other types of cells, like the platelets that normally help blood clot.