Background Information on Dicarboxamide

Go directly to FRAC-Recommendations for Resistance Management for Dicarboxamide Fungicides.

Introduction

The activity of dicarboximide fungicides was first reported in the early 1970's (Fujinami et al. 1971) with the three key commercial products being introduced within three years; iprodione (Lacroix et al. 1974), vinclozolin (Pommer & Mangold 1975) and procymidone (Hisada et al. 1977). They are typically protectant fungicides and although some claims to systemicity have been made (Hisada et al. 1977) they are best regarded as protectant materials. 

Compared to many other classes of fungicide their activity spectrum is relatively narrow, but includes species from the following genera: Botrytis, Sclerotinia, Sclerotium, Monilinia, Alternaria, Phoma, Didymella, Rhizoctonia, Laetisaria (Corticium). Current actives on the market are iprodione, vinclozolin and procymidone. They are sold alone and as components of many co-formulated mixtures. 

Code Target site of action Group name Chemical group Common name Comments
2 MAP/Histidine-Kinase in osmotic signal transduction (os-1, Daf1) Dicarbox-amides Dicarbox-amides chlozinolate iprodione procymidone vinclozilin Resistance common in Botrytis and some other pathogens. Several mutations in OS-1, mostly I356S.

Cross resistance common between the group members

Medium to high risk. See FRAC Dicarboximide Guidelines for resistance management.

References

Fujinami, A., Ozaki, K., Yamamoto, S. (1971) Studies on biological activity of cyclic amide compounds. Part 1. Antimicrobial activity of 3-phenyloxazolidine-2,4-diones and related compounds. Agric. Biol. Chem 35 , 1707 – 1719.

Hisada, Y., Kato, T., Kawase, Y. (1977) Systemic movements in cucumber plants and control of cucumber gray mould by a new fungicide, S-7131. Netherl. J. Plant Pathol. 83, 71 – 78.

Lacroix, L., Bic, C., Burgaud, L., Guillot, M., Leblanc, R., Riottot, R., Sauli, M. (1974) Etude des propriétés antifongiques d'une nouvelle famille des dérivés de l'hydantoine et en particulier du 26019 R.P. Phytiatrie-Phytopharmacie 23 , 165 – 174. 

Pommer, E-H., Mangold, D. (1975) Vinclozolin (BAS 352F) ein neuer Wirkstoff zur Bekämpfung von Botrytis cinerea. Meded. Fak. Landbouwwet. Rijksuniv. Gent 40 , 713 – 722.

Yamaguchi, I., Fujimura, M. (2005) Recent topics on action mechanisms of fungicides. Journal of Pesticide Science 30, 67 – 74.

Site of action

Even after almost 30 years of research the mode of action of dicarboximides is still not certain.  Recent evidence (for review see Yamaguchi & Fujimura 2005) suggests that they interfere with the osmotic signal transduction pathway consisting of histidine kinase and MAP kinase cascades.

Mechanism of Resistance

In B. cinerea and A. alternata , resistance has been attributed to mutations in the histidine kinase genes (Yamaguchi & Fujimura 2005; Dry et al.  2004; Oshima et al. 2002). Similar evidence that the osmoregulatory system is involved in resistance in Cochliobolus heterostrophus is given by Yoshimi et al. (2003). 

Resistant isolates of B cinerea typically show either low, moderate or high levels of resistance according to laboratory assay. Low and moderate levels are normally associated with field isolates, but are still capable of causing disease control failure. Isolates rated as highly resistant in laboratory assay are rarely found in the field.

Cross-resistance

Cross-resistance exists between all dicarboximides although due to differences in activity spectra it may not appear as a perfect relationship with some fungi.  In addition, fungi resistant to dicarboximides were shown to have various levels of resistance to aromatic hydrocarbon fungicides such as chloroneb and tolclofos-methyl, although such cross-resistance is not always present.  In laboratory conditions some cross resistance to phenylpyrroles has been noted but this phenomenon has not been found in field isolates resistant to dicarboximides. 

B. cinerea is a pathogen famous for its ability to become resistant to fungicides.  Resistance to benzimidazoles (MBC fungicides) is common and can be easily accompanied by resistance to dicarboximides and to phenylcarbamates (e.g. diethofencarb).  Double or triple multiple resistance is thus quite possible and must be considered when choosing disease control programs that include such chemistry.  Please note that resistance to dicarboximides does not make fungi resistant to benzimidazoles or phenylcarbamates i.e. there is no cross-resistance between these chemical groups.

Persistence of Resistant Isolates

As a general guide it is accepted that the more resistant an isolate becomes to a dicarboximide fungicide, the less able it is to compete with non-resistant isolates in the wild. However, the picture may not be as definite as suggested.  In a study published by Fourie and Holz in 2003 using isolates of B. cinerea and grapes, both sensitive and resistant germlings colonised fungicide free berries equally well, although sensitive strains penetrated the surface more often.  Fitness decreased as resistance increased. 

When using laboratory selected strains of Sclerotinia minor isolated from lettuce, Hubbard et al. (1997) found that the virulence of resistant strains generated from resistant sclerotia declined with age, occasionally resulting in complete loss of virulence.  Similar results were found by Raposo et al. (2000) when looking at B. cinerea from tomatoes grown in glasshouses.  Sclerotia of resistant isolates survived less well than sensitive ones. There was no relationship found between survival ability and resistance when mycelial survival was considered. 

In contrast LaMondia & Douglas (1997) and Moorman & Lease (1992) report no change in fitness levels of B cinerea isolated from glasshouse crops in the USA.  It is thus wise to assume that reduced fitness is not a phenomenon that can be relied upon as a component of a resistance management program.

References

Dry, I. B., Yuan, K. H., Hutton, D. G. (2004) Dicarboximide resistance in field isolates of Alternaria alternata is mediated by a mutation in a two component histidine kinase gene. Fungal Genet Biol 41 , 102 – 108.

Fourie, P. H., Holz, G. (2003) Fitness on grape berries of Botrytis cinerea isolates belonging to different dicarboximide sensitivity classes. South African Journal of ecology and viticulture, 24, 1 - 10.

Hubbard, J. C., Subbarao, K. V., Koike, S. T., (1997) Development and significance of dicarboximide resistance in Sclerotinia minor isolates from commercial lettuce fields in California . Plant Disease 81, 148 - 153. 

LaMondia, J. A., Douglas, S. M., (1997) Sensitivity of Botrytis cinerea from Connecticut greenhouses to benzimidazole and dicarboximide fungicides. Plant Disease 81, 729 – 732.

Moorman, G. W., Lease, R. J., (1992) Benzimidazole and dicarboximide resistant Botrytis cinerea from Pennsylvania greenhouses. Plant Disease 76, 477 – 480. 

Oshima, M., Fujimura, M. Banno, S., Hashimoto, C., Motoyama, T., Ichiishi, A., Yamaguchi, I. (2002) A point mutation in the two component histidine kinase BcOS-1 gene confers dicarboximide resistance in field isolates of Botrytis cinerea Phytopathology 92, 75 - 80.

Raposo, R., Gomez, V., Urrutia, T., Melgarejo, P. (2000) Fitness of Botrytis cinerea associated with dicarboximide resistance. Phytopathology 90, 1246 - 1249.

Yamaguchi, I., Fujimura, M. (2005) Recent topics on action mechanisms of fungicides. Journal of Pesticide Science 30, 67 – 74.

Yoshimi, A., Imanshi, J., Gafur, A., Tanaka, C., Tsuda, M. (2003) Characterisation and genetic analysis of laboratory mutants of Cochliobolus heterostrophus resistant to dicarboximide and phenylpyrrole fungicides. Journal of General Plant Pathology 69 , 101 – 108.

Resistance Risk and Current Status

Dicarboximides were originally introduced for control of Botrytis cinerea, primarily on vines where they were welcomed due to the occurrence at the time of resistance to MBC fungicides. Resistance management strategies were poorly understood at the time and this inevitably led to overuse of the products such that resistance developed very quickly. Botrytis remains the main fungus at risk although resistance in other genera can easily be found (Table 1). 

Table 1. Fungi resistant to dicarboximides (based on Pommer & Lorenz 1987)

Fungus Year first noted
Alternaria alternata 1980
Alternaria alternata pv. citri 1996
Alternaria brassicicola 2005
Alternaria kikuchiana 1979
Aspergillus nidulans 1977
Botryosphaeria dothidea 2001
Botrytis cinerea 1977
Botrytis elliptica 1992
Botrytis squamosa 1980
Botrytis tulipae 1979
Cochliobolus heterostrophus (mutation) 2003
Cochliobolus miyabeanus 1979
Magnaporthe grisea - (2005)
Microdochium nivale 1990
Monilinia fructicola 1978
Monilinia laxa 1982
Neurospora crassa 1984
Penicillium expansum 1978
Rhizoctonia solani 1979
Rhizopus nigricans 1979
Sclerotinia homoeocarpa 2003
Sclerotinia minor 1983
Sclerotinia sclerotiorum 1979
Sclerotium cepivorum 1984
Ustilago maydis 1978

References

Pommer, E-H., Lorenz, G. (1987) Dicarboximide fungicides. In: Modern Selective Fungicides. Ed H Lyr, Gustav Fischer 1987, pp99 – 118.

Contact

Dr. Andreas Mehl
Chair

Bayer AG, Crop Science Division
Alfred-Nobel-Str. 50,
Building 6240
D-40789 Monheim

Tel: 49-2173-383797
andreas.mehl@bayer.com