SBI Fungicides

SBI-fungicides that inhibit the C14 demethylation step within fungal sterol biosynthesis are known as demethylation inhibitors or DMIs. Chemically, DMIs belong to different chemical groups.  Besides triazoles, numerous imidazoles, pyridines and pyrimidines are also demethylation inhibitors.  All DMIs inhibit fungi by interacting with the same target site, C14-demethylase (erg11/cyp51) and are therefore considered to be cross-resistant with each other.

Typically, DMIs have a broad spectrum of activity against a range of economically important pathogens on arable crops, top fruit, industrial crops, vines, plantation crops, etc.

Like the DMI’s, the Amines also belong to different chemical groups. The first representatives of this group were chemically morpholines. Although representatives of two other chemical groups (piperidines and spiroketalamines) have entered the market, the group designation ‘morpholines’ is still partly used for all three chemical classes. Amines inhibit to a variable degree two target sites within the sterol biosynthetic pathway, the Δ8 → Δ7 isomerase and the Δ14 reductase. Amines have a more narrow spectrum of activity in comparison to the DMIs. They can be used as a solo treatment, but are often used in mixtures with DMIs to control powdery mildews and rusts.

This group is actually represented by two agricultural compounds belonging to two different chemical classes, the hydroxyanilides and the amino-pyrazolinones. Both molecules inhibit the C3-keto-reductase step in ergosterol biosynthesis. KRIs have a narrower spectrum of activity than the DMIs and Amines. The KRIs are specific botryticides which do not show cross-resistance to other classes of anti-Botrytis fungicides nor to other SBI fungicide classes.

The squalene-epoxidase inhibitors are not used commercially as agriculture fungicides.

Resistance to fungicides is a normal phenomenon embodied in the natural process of the evolution of biological systems.  By close co-operation of the agrochemical industry and researchers, advisers and growers we can ensure that fungicides are used optimally and continue to offer the benefits they currently confer.

Resistance to SBI fungicides has been well characterized during the last 20 years.  Issues with SBI performance typically became obvious only after numerous years of intensive use with efficacy degrading stepwise. Following reduced selection pressure, a partial recovery in sensitivity is often observed. The primary mechanism of resistance is the accumulation of several independent mutations in the target site.  Each individual mutation typically causes only a small reduction in sensitivity and it is not until multiple mutations accumulate in an isolate that a large enough reduction in sensitivity is observed to impact efficacy under field conditions.  Resistance to DMIs or Amines is mostly characterized by a slow, step-wise erosion of efficacy over several years of intensive use rather than by a rapid loss of control.

This type of step-wise resistance is called  "multigenic", continuous”, “quantitative” or “shifting” type resistance (Fig. 1).

Fig. 1.  General scheme of shifting-type resistance.

In addition to mutations at the target site, reductions in sensitivity of individual isolates can be also be attributed to overexpression of the cyp51 gene and transport of the fungicide away from the target site by ABC transporters.  It is not clear how important these mechanisms of resistance are under field conditions as they often co-exist with mutations at the target site.

Resistance risk is generally considered to be

Resistance development is typically correlated with a fitness penalty for less sensitive isolates. Partial back-shift is possible if selection pressure decreases.

While compounds within each of the three code groups, G1 (DMIs), G2, (amines) and G3 (KRIs), are cross-resistant with other members within the same group, there is no cross-resistance between members of different groups.  

(No changes in April 2022)

• The recommendations for the use of DMI and amine fungicides in mixture or alternation programmes with different mode of action fungicides remain unchanged. It needs to be emphasized that it is essential for resistance management purposes to follow strictly the manufacturer’s and FRAC recommendations.
• Repeated application of DMI or amine fungicides alone should not be used on the same crop in one season against risky pathogens (e.g. cereal powdery mildews, barley net blotch, scald) in areas of high disease pressure for that particular pathogen.
• Reduced rates of DMIs can contribute to accelerate the shift to less sensitive populations. It is critical to use effective rates of DMIs in order to ensure robust disease control and effective resistance management. DMIs must provide effective disease control and be used at manufacturers' recommended rates.
• When used in mixture, recommended effective rates of the SBI must be maintained.
  Split and reduced rate programmes, using multiple repeated applications at dose rates below manufacturer’s recommendations, provide continuous selection pressure and accelerate the development of resistant populations, and therefore must not be used.
• To ensure good performance and particularly resistance management in situations of even low disease pressure, it is essential to adhere to dosages and spray timings as recommended by manufacturers. Curative applications should be avoided. Application timing has to be appropriate to all mix partners’ characteristics. Mixing with a non-cross resistant fungicide at effective dose rates contributes to a more effective disease control and resistance management.
• The amine fungicides are effective non-cross-resistant partner fungicides for DMIs on cereals for the control of pathogens included in the label recommendation of each respective product.
• Ramularia leaf spot (Ramularia collo-cygni) in barley: Given that there already exist populations of Ramularia collo-cygni in Europe resistant to all main site-specific modes of actions it is recommended to add precautionary a multi-site to ensure robust disease control and an effective resistance management in barley

(No changes in April 2022)

Refer to the general recommendations for SBIs.

In addition to ensure robust disease control and resistance management, it is essential to

• Apply DMI fungicides always in mixtures with effective non-cross resistant fungicides (mix partner shall provide control over the spraying interval).
• Refer to manufacturers' recommendations for rates. Reduced rates must be avoided.
• Apply preventively or as early as possible in the disease cycle.
• Ensure a proper coverage of the treated crop by appropriate and well calibrated application technology (e.g. to ensure penetration into canopy).
• Apply DMI fungicide containing products always at intervals recommended by the manufacturers and adjusted to the disease epidemics. Avoid extended spray intervals.
• Good agricultural practices must be considered to reduce source of inoculum, disease pressure and resistance risk, e.g. no multiple cropping, implement and respect soybean-free periods, consider partially resistant soybean varieties, reduce the planting window, give preference to early-cycle varieties and endorse the destruction of volunteers.

(No changes in April 2022)

• DMIs and amines should be used preventative and curative situations should be avoided.
• The existing strategy for effective disease control and resistance management continues to be successful and the use recommendation is a maximum of 4 applications per season per mode of action. The strategy includes the use of mixtures or alternation with non-cross resistant fungicides.
• To ensure that SBIs can remain the effective basis for control of Erysiphe necator in grape vine, their use should adhere to the full recommended rate (either alone or in mixture) at the recommended timing and application volume and an accurate treatment of each row.

(No changes in April 2022)

• DMI fungicides are not recommended for season-long use and a maximum of 4 DMI sprays either alone or in a mixture is recommended.

• DMIs should be used in mixtures or (block) alternations with a non-cross resistant fungicide. Application of recommended label rates is important.
• Preventative applications should always be the first choice with DMIs. Curative applications are only recommended when accurate disease warning systems are available.

(No changes in April 2022)

•  Use KRIs only protectively.

• Use KRIs only in strict alternation, no block application

• Solo product as part of alternation programmes:
  • Spray programmes with a maximum of 3 treatments per season: max. 1 application with KRIs
  • Spray programmes with 4-5 treatments/season: max. 2 applications with KRIs
  • Spray programmes with 6 and more treatments: at the maximum one third of all Botryticide-applications
• Use in mixtures:
  • Both partners - if applied alone at the dose used in the mixture - must have sufficient activity against Botrytis.
  • Not more than 50% of all Botryticide-treatments should be made with KRIs-containing mixtures.

For sound resistance management, good agricultural practices, including phytosanitary measures and crop protection, should be followed carefully.