Pesticides: Modes of Action and Resistance Management.

The science behind crop protection and the preservation of phytosanitary tools.

Pesticides: Modes of Action and Resistance Management.

In our previous editions, we have explored certifications (ICA, GlobalG.A.P., Rainforest Alliance) and technical aspects such as MRLs that ensure access to international markets. Today, our intention is to delve into one of the most critical technical foundations of modern agriculture: the modes of action of pesticides and resistance management.

More than just applying products to control pests and diseases, the modern farmer must turn their chemical applications and controls into a strategic activity, understanding how pesticides work at the biochemical level, which populations they control, and how to preserve their effectiveness for future applications, seeking to make these more conscious, responsible, and mitigate a latent risk of resistance.

Resistance is not just a technical problem: it is an existential threat to global food security. Each incorrect application accelerates the evolution of resistant populations that can render phytosanitary tools obsolete, forcing the constant development of new molecules and generating significant pressure on the environment and beneficial populations present in the crops.

In this sense, we consider the importance of understanding from the purest definition each of the parameters we will address in this article, allowing those who do not have more precise knowledge to understand it and that it be of great help for future decisions regarding the use of these measures that must be contemplated through an adequate IPM (Integrated Pest and Disease Management).

🔬 Fundamentals

What are Modes of Action?

A mode of action (MoA) is the specific biochemical process or biological function that a pesticide uses to exert its toxic effect on the target organism (pest, weed, or pathogen). It is the exact molecular mechanism by which the active ingredient (AI) interferes with the vital processes of the target organism.

🎯 Components of the Mode of Action

🔑 Site of Action: It is the place where the AI interacts with the organism it is targeting: this can be a protein, enzyme, cell membrane, or process that interferes with the normal biology of the specific organism leading to the death of the pathogen; an example of this is the inhibition of the enzyme acetylcholinesterase in insects causing overstimulation of the nervous system resulting in death.

What is the molecular mechanism or mode of action?

It focuses on the interactions that pesticide molecules have to cause the effect, this occurs through processes such as: enzymatic inhibition, blocking of ion channels, interference with protein synthesis, disruption of metabolic processes, alteration of cellular structures, etc.

📊 Selectivity

It is the ability of pesticides to target specific pests without affecting other organisms that may be beneficial insects or even the main crop in the case of herbicides. A selective pesticide is successful if it causes minimal damage to non-target organisms.

It is important to note that this is one of the fundamental parameters to consider in a good IPM aimed at reducing the negative impact on the surrounding ecosystem of the crop and maintaining an ecological balance.

The selectivity of pesticides is characterized by:

✔︎Allowing differentiation between target and non-target organisms.

✔︎Being the basis of safety for mammals and the environment.

✔︎Being a resource for management and control actions for agricultural use.

At the international level, there are a series of committees formed by organizations and panels of experts and researchers that develop and establish systems to categorize pesticides according to their hazard to human health and the environment, as well as their residues in food where we recall the MRLs and the modes of action for pest control. Basically, the goal of these organizations is to promote safe food trade, protect public health, and coordinate international efforts for the responsible use of pesticides supported by systems such as the WHO (World Health Organization) and criteria from the CODEX ALIMENTARIUS, which we had the opportunity to discuss in our last edition.

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🌐 International Classification Committees

🐛 IRAC - Insecticide Resistance Action Committee

✔︎Mission: Global authority on insecticide resistance management for sustainable agriculture and public health, its task is to classify pesticides according to their mode of action for the control of insects and arachnids (mites) in order to manage pest resistance and coordinate their use in agriculture and control the companies developing these products.
✔︎Last update: 2024
✔︎Main groups: 32 groups and subgroups
✔︎Website: https://irac-online.org/

🍄 FRAC - Fungicide Resistance Action Committee

✔︎Mission: Prolong the effectiveness of fungicides susceptible to resistance and limit crop losses.
It is made up of manufacturers of agrochemical products seeking to prevent resistance of pathogenic fungal microorganisms (Fungi).

✔︎Last update: Poster 2024
✔︎Main groups: 11 main groups (A-U)
✔︎Website: https://www.frac.info/

🌱HRAC - Herbicide Resistance Action Committee

✔︎Mission: It is a committee created to coordinate and communicate effective strategies for proper management of herbicide resistance. It also aims to create cooperation between industry, scientists, and farmers in managing resistant weeds and protecting food production.

✔︎Last update: New classification 2024
✔︎Main groups: 15 main groups (A-O)
✔︎Website: https://hracglobal.com/

Having a greater understanding of how chemical products work on their action targets and with that the basis of the literature to understand their function, it is pertinent then to delve into how resistance to AIs occurs through the genetic evolution of pests and/or phytopathogenic microorganisms:

🧬 Resistance Mechanisms: Evolution in Action

Pesticide resistance is an evolutionary phenomenon where the conditions and hereditary capacity of a population of organisms such as insects, weeds, or phytopathogenic microorganisms to tolerate and survive doses that were previously lethal occur, resulting in a decrease in the effectiveness of the applied product. This occurs due to the genetic selection of individuals that possess a natural resistance, which is passed on to their offspring, allowing the pest population to grow and become less susceptible to the chemical.

🎯 Types of Resistance by Mechanism

1. Site of Action Resistance

Occurs when a pest develops a genetic adaptation that allows it to resist a pesticide by interfering with its specific action mechanism, such as the inhibition of an enzyme or alteration of a receptor site in the pest's body. This phenomenon can prevent successful pest control, especially if pesticides with the same mode of action are used repeatedly, which can lead to an increase in the required dose or ineffective pest control.

2. Metabolic Resistance

It is a common evolutionary mechanism where insects and mites develop internal enzymatic systems to break down or detoxify the active ingredient of the pesticide, converting it into a non-toxic form that can be excreted.

3. Behavioral Resistance

Refers to the ability of a pest to modify or make changes in behavior that reduce exposure to the pesticide in an effort to avoid contact. This type of resistance is a survival strategy that develops when insects detect danger signals and act to avoid absorbing the pesticide, allowing them to survive while susceptible individuals die.

4. Penetration Resistance

Occurs through the modification of the cuticle of insects or their body covering becoming much more resistant to the entry of the pesticide, reducing its absorption and consequently its effectiveness. This type of resistance is mainly limited to insects and does not apply to other pests. In addition to the cuticle, other factors such as the genetic characteristics of the pest, its reproductive capacity, and the way pesticides are applied also influence the development of resistance.

📈 Resistance Evolution:

Regarding acquired resistance, where we could discuss the mechanisms of resistance, it is essential to consider the causes that lead to this phenomenon, so we define the following:

🎯 Factors that Accelerate Resistance:

1. High and Continuous Selection Pressure

Occurs through uncontrolled frequent applications, sublethal doses from concentrations of the AI that do not immediately kill organisms but can cause chronic effects on their growth, behavior, development, fecundity, and survival; these effects may include navigation problems, coordination, damage to the reproductive system, or alterations in metabolism and immunology, and are relevant to understanding the loss of biodiversity and the development of insecticide resistance.

2. Characteristics of the Pest and/or Organism

Pests with short life cycles can reproduce quickly, accelerating the accumulation of resistance genes in their offspring.

Similarly, high fecundity contributes to the rapid evolution of resistance to pesticides, as organisms with resistance genes survive exposure and reproduce causing genetic variability, quickly transmitting the trait to their offspring and overpopulating the population with resistant individuals. This process, accelerated by the repeated application of the same pesticides, can be countered through integrated pest management strategies, such as rotating products with different modes of action and using biological and cultural methods.

3. Characteristics of the Pesticide

✅Pests develop resistance through a unique site of action, preventing the binding of the product and the elimination of the target; characteristics that increase the risk are: high selectivity (a single mode of action), high selection pressure (frequent use), and the evolution of genetic resistance mechanisms that alter or avoid the action of the pesticide at its target site.

✅The high persistence of the pesticide due to its high stability or slow degradation in the environment allows prolonged exposure of the pest to the AI, this constant exposure promotes the selection and concentration of resistance genes in the pest population, as individuals with a greater ability to survive these higher doses manage to reproduce and pass that advantage to their offspring.

✅Systemic pesticides can promote resistance in pests by allowing continuous and prolonged exposure of individuals to low doses of the active ingredient, which genetically selects the most tolerant or even immune organisms. Characteristics that facilitate this resistance include a mode of action that acts on a specific site of the pest, a chemical structure that allows rapid metabolic transformation of the pesticide, or a weakness in the pest's ability to penetrate or neutralize it efficiently.

4. Inadequate Management

✅Repeatedly treating with the same pesticide without rotation or mixing strategies allows resistant organisms to be selected and reproduced.

✅Insufficient doses or contrary to those recommended by the manufacturer may not be enough to reduce pest pressure, which can cause stress in the weaker individuals and survival of the stronger ones.

Next, we propose a resistance management strategy focused on different practices that will allow for better control and reduce the chances of increasing pest and microorganism resistance in the productive environment:

🔄 Resistance Management Strategies

1. Rotation of Modes of Action

📊 Temporal Rotation:
Alternating the use of different products or control methods over time, specifically rotating the modes of action of pesticides instead of just the trade names or active ingredients. This can be done through crop rotation, rotating pesticides (or classes of pesticides) with different mechanisms of action, and implementing a rotation calendar that distributes products throughout the year.

An example of this is: In season 1 apply group A, in season 2 apply group B, in season 3 apply group C, and then return to group A. This way, applications are made with different types of AIs and resistance is limited.

📊 Spatial Rotation:
Involves rotating products (insecticides, fungicides, herbicides) with different modes of action in different areas or plots of the crop to prevent a pest from developing resistance to the same chemical repeatedly. This practice, combined with the use of products with different mechanisms of action, crop rotation, and other integrated pest and disease management (IPM) practices, reduces selection pressure on the pest, maintains the long-term effectiveness of the products, and preserves the population of susceptible insects.

🎯 Rotation Criteria:

✔︎Different sites of action: Never rotate within the same group.
✔︎Equivalent efficacy: Maintain control level.
✔︎Compatibility: With comprehensive phytosanitary program.
✔︎Cross-resistance: Avoid groups with shared resistance.


🔄 Evolutionary Fundamentals of Mode of Action Rotation:

Rotating modes of action constitutes the most important strategy in resistance management because it exploits the fundamental principles of Darwinian evolution: "Natural Selection and survival of the fittest" to maintain the effectiveness of pesticides. This strategy is based on the concept that resistance is specific to each mode of action, and changing the mode of action eliminates the selective advantage of resistant individuals to the previous mode.

2. Mixing Modes of Action

⚗️ Types of Mixes:

🧪Tank Mixes
✔︎Combination at the time of application.
✔︎Flexibility in proportions.
✔︎Check physical and chemical compatibility.
✔︎Consider antagonism/synergism.

🪣Commercial Mixes
✔︎Pre-mixed formulations.
✔︎Optimized proportions.
✔︎Specific registration.
✔︎Greater practicality.

🔬 Principles of Effective Mixes:
1. Components equally effective against target pest.
2. Different modes of action (different molecular sites).
3. Similar persistence to avoid sequential selection.
4. No antagonism between active ingredients.

3. Shelters and Genetic Diversity

🏞️ Untreated Shelters:
✔︎Function: Maintain susceptible population.
✔︎Location: Within or adjacent to the treated area.
✔︎Management: Without application of the target mode of action.

🌾 Crop Diversity:
✔︎Crop rotation: Breaks cycles of specialized pests.
✔︎Trap crops: Concentrate pests for localized control.
✔︎Varietal diversity: Different levels of susceptibility.

🧬 The Importance of Evaluating Resistance

Resistance evaluation represents the scientific foundation upon which all sustainable phytosanitary management strategies are built. Without a robust monitoring and evaluation system, farmers navigate blindly in an ocean of evolutionary pressure where each pesticide application represents a gamble against the fundamental laws of population genetics.

🎯 Early Detection vs. Late Detection

The difference between early and late detection of resistance determines not only the economic viability of management strategies but also the long-term sustainability of available active ingredients. Early detection, when the frequency of resistant alleles is below 1% of the population, allows for the implementation of preventive measures such as rotation of modes of action, adjustment of doses, and modification of application frequencies that can delay or even reverse the development of resistance.

In contrast, late detection, when resistance is already manifested as perceptible control failures in the field, indicates that the frequency of resistant alleles has exceeded 10-20% of the population. At this point, management options are limited to replacing the active ingredient, with the consequent economic and operational implications. Late detection also means that resistance may have spread geographically, greatly complicating containment efforts.


📊 Predictive Value of Monitoring Systems

Well-designed resistance evaluation systems function as early warning systems that provide predictive information about the evolution of pest populations. This predictive capability is based on the understanding that resistance evolves following modelable mathematical patterns, where factors such as selection pressure, heritability of resistance, biological cost of resistance, and gene flow between populations determine the rate of evolution.

An effective monitoring program should include both phenotypic assessments (dose-response bioassays) and genotypic assessments (molecular detection of known mutations). Bioassays provide information about the functional level of resistance in the population, while molecular analyses allow for the detection of resistant alleles even when present at very low frequencies and not yet phenotypically manifested.

📊 Predictive Value of Monitoring Systems

Well-designed resistance evaluation systems function as early warning systems that provide predictive information about the evolution of pest populations. This predictive capability is based on the understanding that resistance evolves following modelable mathematical patterns, where factors such as selection pressure, heritability of resistance, biological cost of resistance, and gene flow between populations determine the rate of evolution.

An effective monitoring program should include both phenotypic assessments (dose-response bioassays) and genotypic assessments (molecular detection of known mutations). Bioassays provide information about the functional level of resistance in the population, while molecular analyses allow for the detection of resistant alleles even when present at very low frequencies and not yet phenotypically manifested.

🌍 Final Reflection

The true value of a chemical application lies not in the immediacy of eliminating a pest but in deeply understanding its purpose, impact, and long-term consequences. Every drop applied to a crop is a decision that transcends productivity: it influences the sustainability of the ecosystem, food security, and the health of those who consume the food we produce.

Therefore, the challenge for the modern farmer is not simply to apply what "works" at the moment, but to ask why it works, how it works, and what footprint it leaves. Researching, training, and making informed decisions is the path for the use of pesticides to become a strategic tool within IPM and not a silent threat that compromises productivity and the future of agriculture.

🙏The invitation: let us not use pesticides as weapons, but as intelligent tools , understanding their mode of action, managing resistance, and respecting the environment. Only then can we achieve truly conscious, resilient, and responsible agriculture towards the environment and future generations.

In our next edition, we will address the topic of using Biocontrol Agents and Bioinputs as a way to exercise good IPM in crops by integrating other non-chemical agents into the productive environment.

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