麻豆传媒

IF AN anthrax attack isn鈥檛 detected quickly, it may be too
late to help the victims. But ways of blocking the bacterium鈥檚 deadly toxin
could one day buy precious time for antibiotics to take effect.

Anthrax toxin is made up of three components called protective antigen (PA),
lethal factor and oedema factor. Individually they are harmless. But after
protective antigen has bound to a receptor on the surface of cells, it combines
with lethal factor and oedema factor. The complete toxin can enter cells, and
when it gets inside immune cells called macrophages, it chews up key enzymes and
kills the cells.

Exactly how this kills people is unclear. Death is preceded by massive
internal bleeding and shock, so one possibility is that the emergency chemical
signals, or cytokines, released by the dying macrophages wreak havoc on the
body鈥檚 blood-clotting systems. Antibiotics are usually useless once symptoms
appear, as enough toxin has already been produced to kill, even if the
antibiotics destroy all the anthrax bacteria.

鈥淭here are a number of clever ways being developed to block the toxin,鈥� says
John Young of the University of Wisconsin-Madison. He and his colleagues have
found the receptor for the toxin. When they synthesised the fragment of this
receptor that sticks to PA, they found that it works as a decoy, mopping up the
antigen before it attaches to cells. The fragment could be used to develop drugs
that do the same job, Young says.

Jennifer Maynard at the University of Texas at Austin and her team have taken
a similar approach, developing super-sticky antibodies that stop PA from
attaching to the receptor. She has 鈥渂red鈥� existing mouse antibodies in the lab
so that they stick to PA 50 times as strongly as before, blocking its ability to
dock with cells, she told an anthrax conference in June. 鈥淔or post-exposure
treatment, antibodies are promising,鈥� she says. The antibodies could also be
developed for use as a highly sensitive, rapid diagnostic test. Maynard is
waiting to publish her findings before going public, but says that tests on rats
are 鈥渆ncouraging鈥�.

Other researchers are targeting different aspects of toxin function. John
Collier and his team at Harvard Medical School have developed molecules that
stop the toxin from assembling, while Robert Liddington鈥檚 group at the Burnham
Institute in California has discovered the structure of lethal factor, the part
of the toxin that destroys cell enzymes. The work could pave the way for rapid
drug development.

Blocking the toxin alone is unlikely to be a miracle cure, according to Harry
Smith of Birmingham University, who discovered the toxin in the 1950s. 鈥淚t would
have to be pretty good to have an effect,鈥� he says.

But extending that crucial time window during which antibiotics can be used
is vital. 鈥淭o have something, even if it鈥檚 not a miracle bullet, should help
quite a bit,鈥� says Maynard.