Fungicides and Mode of Action
We often hear about mode of action when it comes to insecticides, but mode of action is just as important for controlling fungicide resistance.
To effectively manage plant diseases, it is critically important to know the mode of action of labeled fungicides and to understand how to manage fungicide resistance. Mode of action is different than chemical class. Mode of action is the way a chemical works, so chemicals in different chemical classes may have the same or similar modes of action and be causes of resistance.
Most fungicides being developed today have a single-site (specific) mode of action because this is associated with lower potential for negative impact on the environment, including people and other non-target organisms. New fungicides that the EPA classifies as reduced-risk receive priority for review and registration decisions. Due to their single-site mode of action, these fungicides typically have narrow-spectrum activity and are only effective against specific fungal groups.
Thus it is critical to accurately diagnosis diseases and know which labeled fungicides have activity for this fungal group. These fungicides are also at relatively high risk for resistance development compared to those with multi-site modes of action.
Fungicide resistance is a stable, heritable trait that results in a reduction in sensitivity to a fungicide by an individual fungus. This ability is obtained through evolutionary processes. There are two major types of resistance. Knowledge of the type of resistance is important for managing resistance.
When fungicide resistance results from modification of a single major gene, pathogen subpopulations are either sensitive or highly resistant to the pesticide. Resistance in this case often develops quickly and is seen as complete loss of disease control that cannot be regained by using higher rates or more frequent fungicide applications. This type of resistance is commonly referred to as “qualitative” or “complete” resistance. Most pathogens that have developed resistance to methyl benzimidazole carbamate fungicides, such as Cleary’s 3336, and quinone outside inhibitor fungicides, such as Cygnus, have exhibited qualitative resistance. This group includes the powdery mildew fungus affecting verbena and cucurbits.
When fungicide resistance results from modification of several interacting genes, pathogen isolates exhibit a range in sensitivity to the fungicide depending on the number of gene changes. Variation in sensitivity within the population is continuous. Resistance in this case is seen as an erosion of disease control that can be regained by using higher rates, making more frequent applications or switching to an inherently more active fungicide in the same group. Long-term selection for resistance in the pathogen by repeated applications may eventually result in the highest labeled rates and/or shortest application intervals not being able to adequately control the disease. However, it is also possible that the rate is too high for the pathogen to overcome. This type of fungicide resistance, commonly referred to as “quantitative” or “partial” resistance, has developed in some pathogens to demethylathion inhibitor fungicides such as Strike or Eagle.
Managing fungicide resistance is critically important to extend the period of time that an at-risk fungicide is effective. The primary goal of resistance management is to delay development of resistant ones fungal strains rather than to manage resistant after they have been created. Therefore, resistance management programs need to be implemented when at-risk fungicides first become available for commercial use. Resistant strains often persist after use of the affected fungicide group ceases, thus it is generally not possible to resume regularly using these fungicides in the future.
The basic strategy for managing fungicide resistance is to minimize use of fungicides at risk for resistance without sacrificing disease control. This is accomplished by using an integrated program with other fungicides and cultural management practices beginning at first use of at-risk fungicides.
Risk of resistance developing is predicted based primarily on characteristics of the fungicide and the target pathogen. Length of the treatment period and location are also important factors. Risk is considered high when mode of resistance is known (or suspected) to be qualitative or some pathogens have already developed resistance within a few years under commercial use, risk of resistance developing is medium when mode of resistance is quantitative, and risk is low when the fungicide has multi-site activity. Pathogens considered prone to developing resistance have short generation times, produce an abundance of spores readily dispersed by wind and reproduce both asexually and sexually. The longer a crop needs to be treated with fungicides, and thus the greater the number of applications, the higher the chance resistance will develop.
It is critical to use an effective disease-management program to delay the build-up of resistant strains. At-risk fungicides should be used at the manufacturer’s recommended rate and application interval. Using full rates is expected to minimize selection of strains with intermediate fungicide sensitivity when resistance involves several genes (quantitative Á resistance). The lowest labeled use rate for a fungicide is based on efficacy. It is not possible to predict whether a higher rate will be needed to suppress resistance developing to a new product.
Mode of Action
At-risk fungicides should be used in alternation with other at-risk fungicides with different modes of action and/or different chemical groups, and they should be combined or alternated with multi-site fungicides that have a low resistance risk. Some at-risk fungicides are formulated as premix products with other fungicides to manage resistance. The active ingredient thiophanate-methyl, a methyl benzimidazole carbamate fungicide, is combined with chlorothalonil in Spectro (Cleary Chemical Corp.) and with mancozeb in Zyban (The Scotts Company LLC).
Fungal isolates that are resistant to one fungicide are often also resistant to other closely related fungicides, even when they have not been exposed to these other fungicides, because these fungicides all have similar modes of action. This is called cross resistance. For example, although Strike, Eagle and Terraguard have different active ingredients, they are all demethylation inhibitors and thus have the same mode of action, which is to inhibit sterol biosynthesis. The group code number at the top of most new fungicide labels indicates mode of action.
Occasionally, negative cross resistance occurs between unrelated fungicides because the genetic change that confers resistance to one fungicide makes the resistant isolate more sensitive to another fungicide. On the other hand, fungal pathogens have developed multiple resistance to unrelated fungicides.
At-risk fungicides should be used only when needed most. The most critical time to use them for resistance management is early in an epidemic when the pathogen population is small. They should not be used to clean up a disease problem that has become severe.
It is important to consider other crops when developing a fungicide program for managing resistance. Some pathogens infect vastly different plants. The powdery mildew fungus on verbena also infects squash and other cucurbits. Growers have reported control failures with several fungicide groups used for powdery mildew on cucurbits. When one crop could serve as a source of inoculum for a subsequent crop, the rotation plan should be continued between successive crops such that the first at-risk fungicide applied to a crop belongs to a different group than the last at-risk fungicide applied to the previous crop.
Another important component of resistance management is assessing disease control and promptly reporting any loss of efficacy. Labels usually include information about the risk of resistance developing and specific guidelines on resistance management.
The greenhouse is an ideal location for resistance to develop because it is a closed system. It is important to know that while the ability to predict resistance risk is good, it is not perfect. For example, resistance developed quickly to quinone outside inhibitor fungicides, which were initially predicted to Á have low to moderate risk, and one of the first pathogens to develop resistance was considered only moderately prone. Therefore, strategies to manage resistance should be included in all disease management programs.
Fungicide resistance has been documented in Pythium, which causes root rot, and Botrytis, which causes gray mold in ornamental crops. Pythium resistance to phenylamide fungicides has been detected. Strains of Botrytis resistant to methyl benzimidazole carbamate fungicides have become widespread. Neither alternations or mixtures of methyl benzimidazole carbamates with other fungicides were found to suppress resistance development once resistant strains were established. Strains also resistant to dicarboximide fungicides have developed.
While the greenhouse is considered a high-risk location for resistance development, there have been few documented cases of resistance in ornamental crops. This is at least partly due to 1) the diversity of crops typically grown in most greenhouses; 2) the fact that many crops are grown from seed (vegetatively-propagated plants are more likely to harbor pathogens); 3) the crop cycle is usually short so few fungicide applications are needed; 4) fungicides most at-risk for resistance, while highly effective, are generally more expensive than multi-site contact fungicides, thus they rarely are used exclusively; and 5) greenhouse growers have been using a diversity of fungicides and cultural management practices.
Growers should, however, continue to worry about resistance. Considering the potential financial loss due to control failure that can result from fungicide resistance and the long-term impact of losing a fungicide group, prudent growers will not be lax about managing resistance. Also, it is important to realize that lack of detection does not mean resistance has not developed.
Pathogens are tested for resistance when control is greatly reduced and other possible causes can be ruled out. It is not feasible to monitor for resistance due to the cost of testing. Resistance to one fungicide in an integrated program can go undetected when the other components are sufficiently effective. A survey of 135 U.S. greenhouse growers conducted in 1989 revealed that many were using methyl benzimidazole carbamates for gray mold on geranium and not experiencing control failures although resistance was detected in all 13 greenhouses where the pathogen was tested.