The question of whether to tank mix high-risk (HR) fungicides with low-risk (LR) protectant fungicides or the rotation of HR fungicides with LR fungicides remains an open debate. The tank mixing or alternation of fungicides has been widely advocated as a means to delay or minimize the risks of resistance development (Genet et al., 2006; McGrath 2011; Van der Bosch and Gilligan, 2008; van den Bosch et al., 2014; Elderfield et al, 2018), although differences in opinion on whether one is better than the other exist (Genet et al., 2006), or that either method may be an effective means at reducing resistance development (van den Bosch and Gilligan, 2008). The theories behind the rotation or tank mixing of different fungicides follows strategies analogous with managing antibiotic resistance, using methods known as complementary therapy or cycling therapy (van den Bosch and Gilligan, 2008). Fungicide resistance studies with tank mixes or alternations use similar density-independent models as antibiotic resistance and assumes the sensitive and resistant strains to be at low initial densities. Resistance management studies incorporate what is often referred to as takeover time as the evaluation criterion (Van der Bosch and Gilligan, 2008). Take-over time is defined as the time-period in which the fraction of the resistant population passes a critical threshold level, thereby reducing the value of the fungicide for disease control (van den Bosch and Gilligan, 2008).
The concept behind the alternation of fungicides with different modes-of-action is that cyclic selection pressure placed on the fungus should help reduce the buildup of resistant populations, however, this idea has been criticized by numerous authors (van den Bosch and Gilligan, 2008). The argument against the alternation of fungicide chemistries is that this method would only work if it comes with a fitness cost (e.g., the ability to reproduce) associated with the resistant population in absence of selection pressure against the target fungicide (van den Bosch and Gilligan, 2008). Thus, without a fitness cost, the fraction of the resistant pathogen population would not change during the time period when the target fungicide is not used (van den Bosch and Gilligan, 2008). This suggests that resistance development would continue as if there had been no alternation at all, and it would take exactly the same number of fungicide applications of the target fungicide to build up a given level of resistance to that fungicide, although the time for resistance buildup (i.e., take-over time) would be potentially delayed (van den Bosch and Gilligan, 2008). Birch and Shaw (1997) state that one of the advantages to alternation is the possibility of stabilizing selection pressure, if only one of the fungicides were applied at a time.
The concepts behind the tank mixing of fungicides closely follows the concept behind the alternation of fungicides with different modes-of-action. Van den Bosch and Gilligan (2008) using density-dependent models, showed that if no fitness costs exist, mixtures are no different from alternation strategies when comparable doses are used. Tank mixes can be useful if fitness costs exist, but is questionable whether fitness costs would ever be large enough to make mixtures a useful resistance management strategy. Van den Bosch and Gilligan (2008) suggested that tank mixtures deserve attention for their ability to act as insurance in the sense that large scale losses could be avoided if one component of the tank mixture (i.e., the HR fungicide) suddenly fails, and that this is especially important in pathogens where large-scale epidemics (e.g., cucurbit downy mildew) may occur in one year, but not others. Van den Bosch et al. (2014) using empirical and theoretical modeling suggested the following conclusions with using mixtures as a fungicide resistance tactic: 1) adding a multi-site (i.e., LR fungicide) or a specific site (another HR) fungicide to a high-risk fungicide helps reduce the rate of selection against the fungicide(s) with the specific mode-of-action, 2) adding a partner fungicide while reducing the dose of the high-risk fungicide reduces the selection pressure for resistance development without compromising effective control; and 3) while there were few studies done, evidence suggests that mixing two high-risk fungicides is also a useful resistance management strategy. The authors also pointed out that due to the limited research in this area of tank mixes, the lack of these studies should be a warning against over interpreting the findings in their review (van den Bosch et al., 2014). Elderfield et al. (2018) in exploring the alternation or tank mixing of low- and high-risk fungicide programs on lifetime yield (e.g., use) of the high-risk fungicide, in other words, the time period before the high-risk fungicide was no longer economically effective, showed through empirical and theoretical modeling that lifetime yield may be different for different fungicide-pathosystems and that alternation or tank mixing may lead to longer lifetime yields (i.e., use). The authors, based on their evidence, suggest that mixtures of low and high risk fungicides will always be the best resistance management tactic when the objective is optimizing the lifetime yield (i.e., use) of the high-risk fungicide (Elderfield et al., 2018). Gisi et al. (2006) determined in the testing of resistance development in P. viticola (down mildew of grape) using a QoI (FRAC group 11) and protectant (LR) fungicide tank mix that increasing the dose of the non-QoI partner (LR) fungicide in the mixture resulted in reduced selection pressure. The authors also suggested that the choice of non-QoI (LR) fungicide tank-mix partner and its dosage can significantly affect the success of QoI resistance management strategies under practical conditions.
Parnell et al. (2007) suggested that in-field strategies, such as the alternation or tank mixing of fungicides, used to combat fungicide resistance development may be more useful through the restricted deployment of fungicides over large areas. Restrictions on fungicide use in this manner may be extremely beneficial in controlling and managing fungicide resistance development in pathogens such as Podosphaera xanthii (cucurbit powdery mildew) and Pseudoperonospora cubensis (cucurbit downy mildew) which spread over vast geographic areas (i.e., the east coast of the U.S.) each year. Research in the mid-Atlantic region of the U.S. has confirmed the presence of cucurbit powdery mildew populations resistant to FRAC codes 3 and 11 fungicides in recent years. This suggests that QoI- and/or DMI-resistant cucurbit powdery mildew populations could be disseminating up the east coast from the southeast region of the U.S. each production season. Importantly, fungicides in FRAC code 11 are still widely recommended and used in some southern tier states, whereas recommendations and use of FRAC code 11 fungicides for cucurbit powdery mildew control in the mid-Atlantic region have been mostly discontinued in recent years. In order to help combat fungicide resistance development issues such as this in the future, more collaboration between extension personnel from different regions must be done to help establish more defined fungicide resistance management guidelines for large geographic areas such as the south- and northeast regions of the US.
Importance of risk management.
Because certain pesticide chemistries have specific MOA’s there is always a much greater chance for pests (e.g., pathogens, weeds, or insects) to develop resistance. For example, fungi which produce a vast amount of asexual inoculum (i.e. conidia), undergo multiple diseases cycles during a given production season (e.g., powdery and downy mildews), or fungi which have a high probability for sexual reproduction in a field population (e.g., Phytophthora capsici) often have a much greater chance for fungicide resistance development. Importantly, in controlling pathogens where there are but a few, HR fungicide chemistries available for use, selection pressure put on the pathogen may be increased through their overuse. Therefore, the lack of proper chemical rotations (i.e., pesticides with different modes-of-action) or improper tank mixes or rotations may have a dramatic effect on resistance development, especially if these high-risk pesticides are over used or used improperly according to the label.
The grouping of similar chemistries together by their modes-of-action (e.g., FRAC group) and the inclusion of resistance management guidelines on pesticide labels are designed to i) reduce the chances for resistance development and ii) help agricultural producers develop and follow resistance management programs. Although application restrictions and resistance management guidelines have been widely adopted by the chemical industry, the follow-through effects of such guidelines have been left solely to the individual applicator; or extension personnel or crop specialists who help train those applying agricultural pesticides. Jutsum et al. (1998) pointed out that the challenge was to develop fungicide resistance management strategies which were relevant to local production practices. In recent years, the use of FRAC, HRAC and IRAC codes has been widely included in state and regional vegetable commercial production recommendations and promoted and used by extension personnel and crop advisors as education and teaching tools in many production regions of the United States. Even with increased awareness and training, the proper use of these pesticides is ultimately placed upon the end-user (e.g., the farmer/applicator) to make sure that the pesticides are properly applied according to the label rate, its restrictions, and state and federal laws.
Take home thoughts
There is still a lot to learn in the understanding of tank mixing and rotating HR and LR fungicides with each other, and the rotation of HR fungicides with different modes of action on a weekly basis. First, growers need to follow the label. The label is the law. Where appropriate, growers need to rotate HR fungicides with different modes of action (i.e., from different FRAC groups) as much as possible to limit the overuse of any one FRAC group during the production season. In general, tank mixing HR fungicides with LR fungicides will help reduce overall section pressure for resistance development to the HR fungicide. In crops, where there are but one or a few HR fungicides labeled for control of a specific disease, the use of the HR fungicide(s) needs to be done judiciously.
Author citations in parenthesis are from peer-reviewed journal publications.
