There are four groups of fungicides that comprise the Sterol Biosynthesis Inhibitors (abbreviated SBIs) of which three groups (G1 to G3) are used as agricultural fungicides: Demethylation Inhibitors (DMIs), the amines (previously called morpholines), and the Keto-Reductase Inhibitors (KRIs). All groups inhibit targets within the fungal sterol biosynthesis pathway but differ in regard to the precise targets they inhibit so each group has its own FRAC code number.

The SBI-based fungicides represent an important class of agricultural fungicides. They make a major contribution to the world’s agricultural production.

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.