Negative Cross Resistance: past present and potential for the future
This chapter explores the current status of negative cross-resistance (NCR) in the peer-reviewed literature, examines discovery strategies in more detail, discusses how to deploy the resulting NCR compounds, and addresses the potential limitations and possible future opportunities for such an approach in resistance management. NCR has been observed across a variety of species and chemical classes. However, to date, it has not typically been used in wide-scale insect resistance management (IRM). The lack of forthcoming NCR products may be due to logical business models that necessitate the cost effective development of new products due to the needs of the marketplace. In this regard, NCR products will likely only be developed in response to verified resistance to currently marketed high-value products. An additional reason for the lack of NCR compounds may have been the practical limitations in the methodologies needed to efficiently discover them. Development of NCR compounds can be achieved through a variety of methods, for example, use of large-scale screening processes modified from those currently used for screening for novel pesticides. Such screening approaches could involve field resistant insects, or in some specific cases transgenic D. melanogaster expressing the resistance trait. Additionally, advances in molecular cloning and expression of peptides in display technologies could allow for the rapid development of NCR products as soon as resistance occurs in insect populations in the field. Rational design of traditional chemistries as well as proteins is also well established. Thus, field-resistant insects, high throughput transgenic live insect systems, phage display technologies, and rational design approaches, or any combination of these, could be used to assess a wide array of receptor/toxin combinations to model a best fit for NCR toxins useful in the field.
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