Research Reveals Cry1Ab Kills Pests Through Two Pathways; Increasing Sustainability of GE Crops

A new study published in the Proceedings of the National Academy of Sciences (PNAS) and conducted by scientists at the University of Arizona and Nanjing Agricultural University identifies a natural strategy for thwarting pest resistance to Bt proteins. The researchers discovered that the Bt protein Cry1Ab kills pests through two different pathways.

Bt proteins kill insect pests by binding to specific gut receptors after ingestion. However, pests can develop resistance to Bt proteins, and a common mechanism involves changes in gut receptors, specifically ABCC2, ABCC3, and cadherin, that reduce or prevent Bt protein binding.

The scientists used gene editing to disable ABCC2, ABCC3, and cadherin in caterpillars of the Asian corn borer, the major pest of corn in China and in Asia. They investigated how disabling gut receptors ABCC2, ABCC3, and cadherin individually and in pairs affects corn borer caterpillars' susceptibility to Bt proteins Cry1Ab and Cry1Fa. They found that Cry1Ab utilizes two lethal pathways, one requiring ABCC2 and another needing both cadherin and ABCC3. This dual-pathway mechanism makes it significantly harder for pests to evolve resistance to Cry1Ab, as they would need simultaneous mutations in both pathways. In contrast, Cry1Fa uses only the ABCC2 pathway, meaning a single mutation disrupting ABCC2 can lead to high resistance.

These findings were supported by experiments where fall armyworm cells were modified to produce the Asian corn borer receptors. Cells with ABCC2 became susceptible to both Cry1Ab and Cry1Fa, while cells with cadherin and ABCC3 were only susceptible to Cry1Ab, confirming the existence of a second pathway for Cry1Ab that is absent for Cry1Fa.

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