The diamondback moth (Plutella xylostella), one of the world’s most destructive vegetable pests, has evolved resistance to native Bt (Bacillus thuringiensis) toxins, but it can be killed with genetically modified Bt toxins. Photo: Marshall Johnson/University of California, Riverside
One of the most successful strategies in pest control is to
endow crop plants with genes from the bacterium Bacillus thuringiensis, or Bt for short, which code for proteins
that kill pests attempting to eat them.
But insect pests are evolving resistance to Bt toxins, which
threatens the continued success of this approach. In Nature Biotechnology, a research team led by University of Arizona
Professor Bruce Tabashnik reports the discovery
that a small modification of the toxins’ structure overcomes the defenses of
some major pests that are resistant to the natural, unmodified Bt toxins.
“A given Bt toxin only kills certain insects that have the
right receptors in their gut,” explains Tabashnik, head of the UA’s entomology
department in the College
of Agriculture and Life
Sciences. “This is one reason why Bt toxins are an environmentally friendly way
to control pests,” he says. “They don’t kill indiscriminately. Bt cotton, for
example, will not kill bees, lady bugs, and other beneficial insects.”
Unlike conventional broad-spectrum insecticides, Bt toxins
kill only a narrow range of species because their potency is determined by a
highly specific binding interaction with receptors on the surface of the
insects’ gut cells, similar to a key that only fits a certain lock.
“If you change the lock, it won’t work,” Tabashnik says. “Insects adapt through evolutionary change. Naturally occurring mutations are
out there in the insect populations, and those individuals that carry genes
that make them resistant to the Bt toxins have a selective advantage.”
The more a toxin is used, the more likely it is pests will
adapt. Bt toxins have been used in sprays for decades. Crops that make Bt
toxins were commercialized 15 years ago and covered more than 140 million acres
worldwide in 2010, says Tabashnik.
In a joint effort with Alejandra Bravo and Mario Soberón at
the Universidad Nacional Autónoma de México (UNAM), Tabashnik’s team set out to
better understand how Bt toxins work and to develop countermeasures to control
“Our collaborators developed detailed models about each step
at the molecular level,” Tabashnik says, “what receptors the toxins bind to,
which enzymes they interact with and so on.”
Previous work had demonstrated that binding of Bt toxins to
a cadherin protein in the insect gut is a key step in the process that
ultimately kills the insect. Results at UNAM indicated that binding of Bt
toxins to cadherin promotes the next step—trimming of a small portion of the
toxins by the insect’s enzymes. Meanwhile, Tabashnik’s team identified
lab-selected resistant strains of a major cotton pest, pink bollworm (Pectinophora gossypiella), in which
genetic mutations altered cadherin and thereby reduced binding of Bt toxins.
The findings from UNAM and UA considered together implied
that in resistant strains of the pest, naturally occurring genetic mutations
changed the lock—the cadherin receptor—so that Bt toxin—the key—no longer fits.
As a result, the trimming does not occur, the whole chain of events is stopped
in its tracks, and the insects survive.
Says Tabashnik: “So our collaborators in Mexico asked,
‘Why don’t we trim the toxin ourselves, by using genetic engineering to create
modified Bt toxins that no longer need the intact cadherin receptor to kill the
In initial tests, the researchers found that the modified
toxins killed caterpillars of the tobacco hornworm, Manduca sexta, in which production of cadherin was blocked by a technique
called RNA interference. The modified toxins also killed resistant pink
bollworm caterpillars carrying mutations that altered their cadherin.
“Those experiments led us to hypothesize that any insect
carrying a mutant cadherin receptor as a mechanism of resistance would be
killed by the modified Bt toxins,” Tabashnik says.
To find out, the team invited colleagues from all over the
world to participate in an ambitious experiment. “We sent them native and
modified toxins without telling them which was which and asked them to test
both types of toxins against the resistant strains they have in their labs,”
It turned out things are more complicated than the
hypothesis predicted. The modified toxins did not always work on insects with
cadherin mutations, and they worked surprisingly well against some insects
whose resistance was not caused by a cadherin mutation.
“We still don’t know why the modified toxins were so
effective against some resistant strains and not others,” Tabashnik says. “The
take-home message is we need to look at this on a case-by-case basis.”
Tabashnik points out that “based on the lab results, we
think the modified Bt toxins could be useful, but we won’t know until they’re
tested in the field.” He says the results are promising enough that Pioneer, a
major agriculture and biotechnology company, made a significant investment to
pursue the technology.
Through the UA’s Office of Technology Transfer, the UA’s
stake in the technology has been licensed to UNAM, which in turn selected
Pioneer as their commercial partner in exploring its potential for
“At the very least, we’ve learned more about the pests and
their interactions with Bt toxins,” Tabashnik says. “In a best-case scenario,
this could help growers sustain environmentally friendly pest control.”