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9-Misc: New target organisms for Bt toxins found

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SOURCE: University of California - San Diego, USA, Press Release
DATE:   Feb 19, 2003

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Biologists at the University of California, San Diego have discovered
that Bacillus thuringiensis, or Bt - a bacterium that produces natural
protein insecticides that have been used by organic farmers for five
decades - can also produce similar natural proteins that kill nematodes.

The discovery could pave the way for the development of an inexpensive
and environmentally safe means of controlling the parasitic roundworms
that each year destroy billions of dollars in crops, cause debilitating
diseases in farm animals and pets, and now infect a quarter of the
world's human population. The scientists' findings appear in the March 4
issue of the Proceedings of the National Academy of Sciences, which is
making their paper available this week in its early online edition.

Major parasitic roundworm diseases in humans include ascariasis, which
affects 1.5 billion people worldwide; hookworm, which infects 1.3 billion
people; and elephantiasis, which affects 120 million people. Other
parasitic nematodes are major agricultural pests, affecting such
economically important crops as corn, soybeans, potatoes and tomatoes.
They are also a problem in horses, livestock and pets.

Scientists have been increasingly concerned about parasitic nematodes
developing resistance to the drugs now being used to treat or prevent
their infestations. But an even larger impediment to the widespread use
of those drugs is that they are costly, as any pet owner who must
purchase heartworm preventative knows.

That's not the case with Bt toxins, which have played an important role
in controlling insects, such as mosquitoes that carry disease, in third
world countries and are now being used in genetically modified cotton,
corn and other crops to control caterpillars and beetles.

"Not only are Bt toxins relatively easy to make, but they are extremely
safe to humans and vertebrate animals," says Raffi V. Aroian, an
assistant professor of biology at UCSD who headed the study. "All of the
data show that these crystal proteins are non-toxic to animals with
backbones. What our discovery suggests is the potential for preventing
not only billions of dollars worth of agricultural damage from parasitic
roundworms each year, but also the potential for preventing some
important and debilitating forms of human and animal disease."

The discovery was made by a team of biologists working in Aroian's
laboratory - Jun-zhi Wei, Kristina Hale, Cynthie Wong and Su-chiung Fang.
Nematologists Lynn Carta of the USDA's Agricultural Research Service in
Beltsville, Md., and Edward Platzer of UC Riverside also contributed to
the study, which was supported by the National Science Foundation,
Burroughs-Wellcome Foundation, the Beckman Foundation and the University
of California BioSTAR program.

The UCSD biologists sought to investigate the potential for Bt toxins -
which attack and dissolve the intestines of their insect hosts - as an
anti-roundworm agent after determining that a specific Bt crystal protein
they were studying, Cry5B, destroyed the intestines of the common
laboratory nematode, C. elegans. They also found in previous experiments
that two other Bt crystal proteins, Cry6A and Cry14A, had the ability to
significantly reduce the ability of C. elegans to produce numerous young.

To determine whether these effects applied to other nematode species, the
scientists investigated the effects of seven crystal proteins related to
and including Cry5B and Cry6A, on five phylogenetically diverse free-
living nematode species that feed on bacteria - C. elegans, Pristionchus
pacificus, Panagrellus redivivus, Acrobeloides sp. and Distolabrellus
beechi - and the free-living stage of a different species -
Nippostrongylus brasiliensis - which in other stages is an intestinal
parasite in rats. The researchers discovered that all six of these
nematodes, which were also chosen because they are fairly diverse and can
be raised easily in the laboratory, are susceptible in varying degrees to
the crystal proteins - either by killing them, damaging their intestines
or reducing their brood size. They also found that not all of the related
crystal proteins killed nematodes, suggesting that only a limited number
of the known crystal proteins target this invertebrate phylum.

The UCSD discovery represents the first time scientists have verified
that Bt toxins can widely affect nematodes. "Our finding that there is a
family of crystal proteins that can kill nematodes is the first in the
scientific literature, although it was recognized in patents filed by the
Mycogen Corporation," says Aroian. "And the most important part of the
discovery is that we can kill at least one nematode that is a mammalian
parasite, which suggests that these crystal proteins can be used against
nematode parasites in humans."

Whether such Bt crystal proteins can negatively affect some or all of the
many species of beneficial soil-dwelling nematodes that control insect
pests will require further study before they can be widely used on
agricultural crops. However, the Bt strains that produce these crystal
proteins, which multiply in the intestines of nematodes, suggest to the
scientists that soil-dwelling nematodes may have contributed to the
evolution and spread of the Bt bacterium.

"It seems plausible that a soil bacterium might take advantage of the
fact that soil nematodes use bacteria as a food source and evolve crystal
proteins to help it propagate inside the host nematode once its spores
and crystals are ingested," the scientists write.

"The most important conclusion of these studies is that Bt crystal
proteins have potential in controlling nematode pests that infect animals
and plants," the authors add in their paper. "In particular, the
effectiveness of Cry5B, Cry14A and Cry21A against the free-living stage
of an animal parasite, N. brasiliensis, is promising. Although it remains
to be seen whether these toxins are effective against other parasites or
against nematodes in parasitic stages, these results demonstrate that a
parasitic nematode can express the proper molecular elements for
responding to Bt toxins. Given the very low toxicity of Bt crystal
proteins in general toward vertebrates, Bt crystal proteins may one day
provide safe, cost-effective control of nematode parasites, such as those
that infect over a quarter of the human population."

To learn more about Bt crystal proteins and their use, visit an
informational site on the subject created by the Aorian laboratory at

Media Contacts: Kim McDonald (858) 534-7572
Comment: Raffi V. Aroian (858) 822-1396
Photo Credit: J. Wei and K. Hale, UCSD