Resistance shapes the discovery of new insecticides
Spider venoms are a complex chemical cocktail made up of hundreds of different compounds. We expect spider venoms to be excellent insect killers, since that’s what they are designed to do in nature.
Individual spider venom components are small proteins, called peptides, which have the pharmacological properties of stability and efficacy that are needed for new insecticides. Once we have isolated those compounds of interest we are able to make them recombinantly, that is, using bacterial or yeast expression systems so the venom is no longer needed.
By using hundreds of millions of years of evolution as a starting point, we can use chemistry to adapt the molecular scaffolding of these peptides to be more effective, more selective, and safer to use.
New insecticides are designed to be very specific in what they target, namely, insects. Many insecticides target only the insect nervous system, which is very different from the one found in vertebrates (including humans).
Just as with antibiotics, insecticide resistance develops when the same type of insecticide is overused. This leads to a handful of targets being exploited repeatedly, which means the bugs develop workarounds to insecticides that share a molecular target.
Tracking resistance
An industry group, the Insecticide Resistance Action Committee, was formed to track insecticide resistance and to develop a classification scheme for all known insecticide targets. There are currently twenty-six classes based on how the insecticide acts, plus another category for unknown or uncertain modes of action.
Based on the molecular target, insecticides that target acetylcholinesterase, chloride channels, or sodium channels are 65 percent of the compounds with demonstrated resistance.
Implications for human health
One example of the need for new insecticides with new targets is for human health.
Malaria is a life-threatening human disease that is caused by a parasite. This parasite is transmitted to humans through a bite from a mosquito infected with the malaria parasite.
Although it is a preventable and curable disease, it remains a serious health concern in many subtropical areas. In 2012, malaria was the cause of death for 627,000 people, mainly African children.
Mosquito control is the most effective way to reduce malaria transmission, but the World Health Organisation has approved only four insecticides for this purpose.
Further complicating matters, most mosquitoes are resistant to one or more types of insecticide — in some areas, mosquitoes are resistant to all four approved insecticides.
Further complicating matters, there are only two modes of action for these four different compounds: pyrethroids (IRAC Class 3A) and organochlorines (3B) both modulate the insect sodium channel, and carbamates (1A) and organophosphates (1B) inhibit acetylcholinesterase.
Insecticide resistance is a problem that affects us all.
Livestock are affected by buffalo flies; farmers and customers are familiar with the total devastation caused by fruit flies; malaria mosquitoes and bed bugs are becoming more resistant to existing chemicals. Even our pets are affected: fleas and ticks are continuing their march, leading to a need for newer, often more expensive synthetic chemistries.
The price of insecticide resistance — in the form of R&D costs for new compounds — is passed from chemical companies, to farmers, to consumers.
What is the solution?
Combinations of new technologies, like integrated pest management (IPM) and compatible insecticides, is a promising solution to insecticide resistance.
This IPM insecticide technique requires that growers are trained in the appropriate use of insecticides. It also demands that we have chemical solutions available that will be effective if their crops are attacked above a predetermined economic threshold.
The goal of our research is to provide this type of safe, environmentally friendly chemical control option for difficult-to-treat insect pests. These compounds are designed to be effective as a stand-alone product, or for use in tandem with natural enemies as part of an IPM program.
Margaret C. Hardy is postdoctoral Research Fellow at University of Queensland.This story is published courtesy of The Conversation(under Creative Commons-Attribution/No derivatives).
