Smarter toxins help crops fight resistant pests
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.
Said 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 pests?’”
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 said.
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,” Tabashnik said.
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 said. “The take-home message is we need to look at this on a case-by-case basis.”
Tabashnik pointed 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 said the results are promising enough that Pioneer, a major agriculture and biotechnology company, made a significant investment to pursue the technology.