Introduction and General Information
The FRAC-SBI (formerly DMI) working group was set up in 1982. The group meets annually to review monitoring data and to agree on use recommendations for SBI fungicides.
Definitions - SBI-Fungicides
There are four groups of fungicides that comprise the Sterol Biosynthesis Inhibitor's (abbreviated SBI's) 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.
Overview on Sterol Biosynthesis Inhibitors
Code Group G1: Demethylation Inhibitors (DMIs, FRAC Code #3, SBI class I)
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, DMI's have a broad spectrum of activity against a range of economically important pathogens on arable crops, top fruit, industrial crops, vines, plantation crops, etc.
|3 ||G1: |
C14-demethylase in sterol biosynthesis (erg11/cyp51)
|DMI-fungicides (DeMethylation Inhibitors) |
|piperazines ||triforine || There are big differences in the activity spectra of DMI fungicides. |
Resistance is known in various fungal species. Several resistance mechanisms are known incl. target site mutations in cyp51 (erg 11) gene, e.g. V136A, Y137F, A379G, I381V;
cyp51 promotor; ABC transporters and others.
Generally wise to accept that cross resistance is present between DMI fungicides active against the same fungus.
DMI fungicides are Sterol Biosynthesis Inhibitors (SBIs), but show no cross resistance to other SBI classes.
See FRAC SBI Guidelines for resistance management
|pyridines ||pyrifenox |
|pyrimidines ||fenarimol |
| imidazoles || imazalil |
| triazole || azaconazole |
| triazolinthiones ||prothioconazole |
Code Group G2: Amines (FRAC Code #5, old SBI class II)
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 DMI’s. They can be used as a solo treatment, but are often used in mixtures with DMI's to control powdery mildews and rusts.
|5 ||G2: |
△14-reductase and △8→△7-isomerase in sterol biosynthesis
| amines |
(SBI: Class II)
| morpholines || aldimorph |
| Decreased sensitivity for powdery mildews. |
Cross resistance within the group generally found but not to other SBI classes.
Low to medium risk.
See FRAC SBI Guidelines
for resistance management.
| piperidines || fenpropidin |
| spiroketal-amines || spiroxamine |
Code Group G3: Keto-reductase inhibitors (KRIs, FRAC Code #17, SBI Class III)
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 DMI’s 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.
| (SBI: Class III) || hydroxyanilides || fenhexamid || Low to medium risk. |
Resistance management required.
| amino-pyrazolinone || fenpyrazamine |
Code Group G4: Squalene-epoxidase inhibitors (FRAC Code #18, SBI class IV)
The squalene-epoxidase inhibitors are not used commercially as agriculture fungicides.
| 18 |
squalene-epoxidase in sterol biosynthesis
| (SBI: Class IV) || thiocarbamates || pyributicarb || Resistance not known, fungicidal and herbicidal activity |
| allylamines || naftifine |
| Medical fungicides only |
Resistance to SBI 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 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 low to medium (amines, KRIs) or medium (DMIs)
Resistance development is typically correlated with a fitness penalty for less sensitive isolates. Partial back-shift is possible if selection pressure decreases.
Cross Resistance among SBI - fungicides
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.