Genetic strategy reverses insecticide resistance

الاستراتيجية الجينية تعكس مقاومة المبيدات الحشرية Nature Communications That gene drives engineered for inheritance bias called allele drives can be applied in the absence of pesticide treatment to restore susceptibility to pesticides and normal, balanced levels of the insect population. Credit: Bier Lab, University of California, San Diego” width=”800″ height=”530″/>

Reversing insecticide resistance with a new type of genetic drive: Treating fields with insecticides leads to the emergence of insecticide-resistant insect pests and reduces the diversity of beneficial insects. A new proof-of-principle study was published in Nature Communications He demonstrates that genetic-biased genetic drivers called alleles can be applied in the absence of pesticide treatment to restore susceptibility to pesticides and normal, balanced levels of insect populations. Credit: Bier Lab, University of California, San Diego

Pesticides play a key role in efforts to counter the global impacts of malaria spread by mosquitoes and other diseases, which cause an estimated 750,000 deaths each year. These insect-specific chemicals, which cost more than $100 million to develop and bring to market, are also essential to controlling insect damage to crops that are challenging to food security.

But in recent decades, many insects have genetically adapted to become less sensitive to the effectiveness of insecticides. In Africa, where long-lasting insecticide-treated nets and indoor spraying are major weapons in malaria control, many mosquito species across the continent have developed resistance to the insecticides reducing the effectiveness of these key interventions. Climate change in certain regions is expected to exacerbate these problems.

Biologists at the University of California, San Diego have developed a method that reverses insecticide resistance using CRISPR/Cas9 technology. As shown in Nature CommunicationsIn this study, researchers Bhagashree Kaduskar and Raja Kushwa, Professor Ethan Beer of the Tata Institute of Genetics and Society (TIGS) and their colleagues used a gene-editing tool to replace the insecticide-resistance gene in fruit flies with the naturally infested form of insecticide, an achievement that could significantly reduce the amount of pesticides used.

“This technique can also be used to increase the proportion of a naturally occurring genetic variant in mosquitoes that makes them resistant to transmission of parasites or malaria parasites,” said Pierre, professor of cell biology and growth in the Department of Biological Sciences at the University of California, San Diego. The author of the paper.

The researchers used a modified type of gene drive, a technology that uses CRISPR/Cas9 technology to cut genomes at target sites, to spread specific genes between populations. When one parent passes genetic elements to its offspring, the Cas9 protein cuts the chromosome from the other parent at the corresponding locus and the genetic information is transcribed to that locus so that all offspring inherit the genetic trait. The new gene drive includes an add-on previously designed by Bier and colleagues to bias the inheritance of simple genetic variants (also known as alleles) by cutting an unwanted genetic variant (eg, insecticide-resistant) and simultaneously replacing it with the preferred variant (eg. sensitive to insecticides).

In the new study, the researchers used an “allelic drive” strategy to restore genetic susceptibility to insecticides, similar to insects found in the wild before they developed resistance. They focused on an insect protein known as voltage-gated sodium channel (VGSC) which is the target of a widely used class of insecticides. Resistance to these insecticides, which is often called resistance to knockdown, or “kdr,From mutations in vgsc The gene that no longer allows the insecticide to bind to the target of the VGSC protein. The authors substituted a resistant material Energy Mutation with its natural counterpart exposed to pesticides.

Starting from a population of 83% Energy alleles (resistant) and 17% normal (pesticide sensitive) alleles, the allelic drive system overturned that ratio to 13% resistant and 87% wild type in 10 generations. Bier also points out that adaptations that confer insecticide resistance come at an evolutionary cost, making those insects less favorable in a Darwinian sense. Thus, pairing the gene drive with the selective advantage of the most suitable wild-type genetic variant results in a highly efficient and collaborative system, he says.

Similar allele-driven systems can be developed in other insects, including mosquitoes. The proof-of-principle adds a new method to pest and vector control toolkits that can be used in conjunction with other strategies to improve insecticide-based or parasite-reducing measures to reduce the spread of malaria.

“Through these allelic replacement strategies, it should be possible to achieve the same degree of pest control with much less use of insecticides,” said Pierre. “It should also be possible to design self-eliminating versions of drivers of alleles programmed to act only temporarily in a population to increase the relative frequency of the desired allele and then disappear. The drivers of locally operating alleles can be reapplied as necessary to increase the abundance of a preferred trait that naturally occurs with the final endpoint. Which is not to leave any GMOs in the environment.”

Craig Montell (UC Santa Barbara), a co-author on this study, suggested that “an exciting possibility is to use allele drivers to deliver new versions of VGSCs that are more sensitive to pesticides than wild-type VGSCs.” “This could allow lower levels of pesticides to be introduced into the environment to control pests and disease vectors.”

CRISPR-based ‘allelic drive’ allows gene editing with selective precision and broad effects

more information:
Bhagyashree Kaduskar et al, Reversing insecticide resistance using drive alleles in Drosophila melanogaster, Nature Communications (2022). DOI: 10.1038 / s41467-021-27654-1

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