Fungicide Resistance Action Committee

Background Information on Phenylamides

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


The phenylamides are a highly active class of fungicides specifically controlling plant pathogens of the Oomycetes (the downy mildews of the Peronosporales and Sclerosporales, as well as most members of the Pythiales (e.g. Phytophthora and Pythium spp.) and Saprolegniales; Gisi 2002). They penetrate the plant tissue rapidly and are translocated acropetally within the plant.  Phenylamide fungicides have been in commercial use since 1978. The following active ingredients are classified as phenylamides: metalaxyl, metalaxyl-M (=mefenoxam), furalaxyl and oxadixyl, benalaxyl and benalaxyl-M (=kiralaxyl) and ofurace (Gisi and Ziegler 2002; Müller and Gisi 2007).

Code Target site of action Group name Chemical group Common name Comments
4 RNA Polymerase I PA-fungicides (Phenylamides) acyl- alanines benalaxyl
furalaxyl metalaxyl metalaxyl-M (=mefenoxam)
Resistance and cross-resistance well known in various Oomycetes but mechanism unknown.

High risk. See FRAC Phenylamide Guidelines for resistance management.
oxazolidinones oxadixyl
butyrolactones ofurace

Despite the presence of Phenylamide-resistant isolates in major target pathogen populations, they continue to be used by growers as effective tools to manage disease when used in accordance with sound resistance management programs (see General Use Recommendations).  The use recommendations are well established and do not create significant controversy among member companies, officials and advisors. Current sensitivity monitoring data are produced by only a few research groups in industry and academia. The presence of resistant subpopulations at varying proportions is well documented in several plant pathogen species of Oomycetes on a range of crops worldwide (Gisi and Cohen 1996; Gisi and Sierotzki 2008; FRAC Resistance Survey List, However, sensitive subpopulations have not disappeared, even though PA-containing products have been used continuously in similar quantities and intensities over the past 30 years. This strongly suggests that the recommended anti-resistance strategies are successful and that biological processes (e.g. sexual reproduction, fitness) of the pathogens may contribute to equilibrate sensitivity in populations. Sampling and testing methods for resistance monitoring have been published through FRAC in 1992 (EPPO Bulletin 22, 297-322) and are still valid.

Site of Action and Mechanisms of Resistance

The PA-fungicides inhibit rRNA biosynthesis (polymerase complex I) in the target pathogens. The mechanism of resistance may involve one (or two) major gene(s) and potentially several minor genes. The target gene and the site of mutation(s) in the genome have not been mapped so far. Therefore, there are no molecular methods available for the detection of resistance.

Sensitivity of field populations



Resistant isolates of Phytophthora infestans and Plasmopara viticola existed at low proportions in wild type populations before PA fungicides were used commercially (1977/78) suggesting that recurrent mutations give rise to resistant individuals at different locations and time periods (Gisi and Cohen 1996). Resistant isolates were selected through the use of PAs, increased in frequency, survived during over-wintering periods and migrated to other regions through transport of sporangia in rain droplets and infected plant material (tubers, seedlings). Resistant isolates can compete successfully with sensitive isolates even in the absence of PA treatments. Therefore, resistant isolates can be detected in current field populations that were treated with PAs previously or which remained untreated.

Samples for sensitivity analyses should be taken as early in the epidemic cycle as possible. Those taken towards the end of the season will provide results which are a result of selection, migration, mating and competition which occurred during the current season's epidemic. As a consequence, resistance frequencies are often overestimated. Standard sensitivity test methods (e.g. leaf disc assay) provide a fully resistant response to PAs (used as active ingredients) when as little as 1% of the sporangia in bulk samples of field populations are resistant (Sozzi et al. 1992). Since sensitivity tests are made with active ingredients of PAs but products are used for disease control in the field in mixture with multi-site fungicides (e.g. dithiocarbamates like mancozeb), there is no direct correlation between sensitivity test results in the laboratory and product performance in the field.

The current sensitivity test methods provide valuable information on the distribution of isolates over a certain time period in a given agronomic area but should not be used to predict product performance. In most cases mixed populations can be controlled adequately by PA-containing products if the proportion of resistant isolates is not too high and if the number of applications is limited (see use recommendations).

There is full cross resistance among all members of PA fungicides but there is no cross resistance between PAs and fungicides of other chemical classes like cyanoacetamide oximes (cymoxanil), QoIs (e.g. azoxystrobin, famoxadone), phosphonates (fosetyl-Al), carboxylic acid amide (CAA) fungicides (dimethomorph, iprovalicarb, mandipropamid), carbamates (propamocarb), dinitroanilines (fluazinam) and multisite inhibitors (e.g. dithiocarbamates like mancozeb).

Potato and tomato late blight (Phytophthora infestans)

The sensitivity of populations fluctuates from year to year and within the season. In many cases, sensitive isolates predominate early and resistant isolates predominate late in the season for both PA-treated and untreated fields. In most countries of Western Europe (e.g. France, UK, Netherlands, Belgium, Germany, Switzerland), the proportion of resistant isolates have remained more or less stable for many years but increased again during 2003-2006. By 2007 the proportion of resistant isolates reached high levels (50 to 80%), except for Denmark, where it remained low (about 10%). Such results depend very much on the dynamics of epidemics and on when in the season the samples were collected (high frequency of resistance late in the season) and on how many samples were tested (more reliable results when more than 20 samples per agronomic area are tested). Resistance frequencies can change dramatically within a few years as it was reported for Israel (Cohen, 2002) and Japan (FRAC), where the proportion of resistant isolates in field populations declined significantly during this time and was very low in 2006.

Resistant isolates may be present in field populations in high proportions at the end of the season, and may be lower in frequency at the beginning of the next season. Therefore, over several years, resistant isolates may be in a “dynamic equilibrium” with sensitive isolates. Dynamics of resistance evolution are driven not only by selection through PA fungicides; equally important are biological processes during pathogen development (e.g. patchy occurrence of sexual recombination, effective migration of sporangia and infected plant material over large distances and changes in virulence, fitness and aggressiveness). The presence of resistant isolates has been confirmed in all parts of the world but the frequencies in populations are not well documented. The phenotypic and genotypic structures of current field populations suggest that they may emerge from local processes in addition to long distance transport. Isolates with an intermediate response to PAs can emerge through sexual recombination.

There is no genetic linkage between resistance to phenylamides and mating type (A1, A2). Sensitive, intermediate and resistant phenotypes can be represented in both the A1 as well as in the A2 mating types. The proportion of A2 mating type isolates collected from commercial potato fields has been low in many European countries (e.g. UK, France, Germany, Switzerland) until about 2000, whereas in other countries such as Mexico, the Netherlands and Scandinavia it reached 50% and more. However, since about 2004, the proportion of A2 mating type isolates increased significantly in Western Europe (except Denmark where A1 is still frequent) reaching 50 to 90% in 2007. By coincidence, the majority of these A2 isolates were resistant to PA fungicides. In Israel, the A1/A2 proportion changed in the last 30 years from initially almost 100/0 to 0/100 to again 100/0, the majority of recent isolates being A1 and PA-sensitive (Cohen 2002 and pers. comm.).

On tomatoes in private gardens (e.g. France), the proportion of A2 mating type isolates has been much higher than on potato (Knapova and Gisi 2002). Although populations from tomato and potato can be separated from each other genotypically (e.g. by SSR markers), there is a certain proportion of overlap in field populations. The aggressiveness of isolates is highest on the host of their origin and can be significantly lower for isolates collected from potato when tested on tomato. Tomato isolates can be rather aggressive on both hosts. Therefore, highly aggressive A2 isolates may jump easily from infected tomato to potato.

In countries outside Europe, e.g. the USA, Mexico and some Asian countries, P. infestans isolates have been tested for sensitivity to PA fungicides, mating type and molecular markers in the 1990’s (e.g. Fry et al. 1993). The “old” genotypes were reported to have been replaced in the USA, Canada and elsewhere by new genotypes (e.g. US 8 genotype, mostly A2 type), as a result of migration and recombination (Godwin et al. 1998). However, no relevant results on sensitivity of population have been published recently.

Major changes in the genotypic structure of P. infestans populations have occurred in Western Europe starting about in 2004. These changes became visible by using new molecular techniques, e.g. SSR (simple sequence repeats) also known as microsatellites (Knapova and Gisi 2002; Cooke and Lees 2004; Lees et al. 2006). When isolates collected in Europe in 1997 were compared with isolates from 2007, it can be demonstrated that the “old” A1 SSR genotypes (sensitive or resistant to PAs) significantly declined, two “new” A2 SSR genotypes (PA-resistant) emerged and became dominant (more than 50% in population), but also few PA-sensitive A1 SSR genotypes emerged in the same time period (Syngenta results and results collected by D. Cooke,

It is an ongoing discussion whether today’s P. infestans isolates in Europe are more aggressive than 10 years ago.  Although a higher aggressiveness was claimed for recent P. infestans isolates in the Netherlands (e.g. Flier and Turkensteen 1999), isolates collected in the UK, France and Switzerland in 2006 were not more aggressive than isolates from 1997 and 1979 (Syngenta results).

Several important questions about the driving forces for changes in recent P. infestans populations in Europe are still unsolved, e.g. which are the main selecting forces for new genotypes (cultivars, climate, fungicides?), how important are sexual and parasexual processes, and local and long distance transport (sporangia, infected seed tubers, tomato plants as inoculum)? However, P. infestans populations seem to remain largely clonal.

Grape downy mildew (Plasmopara viticola)

Much less information on resistance to PAs is available for this pathogen compared to P. infestans. In countries where sensitivity analyses have been conducted recently (e.g. France, Switzerland, Spain, Germany), the proportion of resistant P. viticola isolates has remained high (50 – 80 %) but more or less stable for many years (Gisi and Sierotzki 2008). In northern Italy, resistance was reported to be low. In many other countries, PA-resistant isolates were detected, although their proportion is not well documented. Sensitivity monitoring efforts are continued and data from most recent years (2017/8) confirm the above described situation, however, in respect to it, it has been agreed to adapt the recommendations accordingly (see below).

Since P. viticola undergoes sexual recombination every winter, the genetic diversity of the primary inoculum is very high (Gobbin et al. 2007) and resistance is inherited according to Mendelian rules, i.e. all F1 progeny isolates are intermediate in sensitivity. The proportion of sensitive, intermediate and resistant isolates in F2 progeny should then be 1:2:1 (theoretical) but has been observed to be 1:3:2 (progeny of cross under laboratory conditions) and 1.5:2:1 (selected field populations in France, Gisi et al. 2007). The sensitivity of field populations fluctuates from year to year and within the season (Gisi 2002). Sensitive, intermediate and resistant isolates can be detected in fields that were treated with PAs or remained untreated and are often in a “dynamic equilibrium” with each other. In general, the proportion of sensitive isolates declines during the epidemics every year (Gisi and Sierotzki 2008). Dynamics of resistance evolution are driven not only by selection of PA fungicides; the type of Mendelian inheritance and the genetic background of resistance as well as the fitness of R-isolates and rate of migration are equally important.

Pythium species in corn, vegetables and other arable groups

PA sensitivity monitoring program from many years from EU highlighted that the population is broadly sensitive with some areas where resistance is present:

  •             Mainly found in Belgium
  •             Single cases in France, Netherlands, Germany and Spain
  •             No resistance has been found in Hungary, Romania and Italy

PA resistance is disruptive in Pythium spp, although intermediate phenotypes can also be found.

Individuals of Pythium spp with disruptive resistance towards PA can not be controlled with PAs.

The majority of PA resistance isolates belong to Pythium ultimum.

Monitoring data suggest that the oomycete control in the previous crop can influence the frequency in the following crop: PA resistance is mainly detected in situation where the previous crop were vegetables, like spinach, leeks, beans, but also in melons and potato. No PA resistance has been detected in cases when cereals, sugarbeet, rape or grassland were planted previously.

Based on the discussed and the agreed assessment of the situation new recommendations were established (see PA-recommendations-page)

Other pathogens

The presence of resistant isolates in field populations has been confirmed in several other pathogens including Pseudoperonospora cubensis (e.g. Israel, USA, Australia), Peronospora tabacina (e.g. USA), Peronospora pisi (e.g. New Zealand), Bremia lactucae (e.g. USA, UK, Italy), Pythium spp. (turfgrass in USA) and other pathogens on a range of crops in several countries (Gisi 2002; FRAC Resistance Survey List, However, the proportion of resistant isolates in field populations is not well documented. Resistance levels are not uniform and do not necessarily correlate with product performance problems.

Above mentioned information is agreed among the contributing companies and is publicly available. More detailed data or information need to be requested from the respective company directly.


Cohen Y. 2002. Populations of Phytophthora infestans in Israel underwent three major genetic changes during 1983 – 2000. Phytopathology 92:300-307. 

Cooke DEL, Lees AK. 2004. Markers, old and new, for examining Phytophthora infestans diversity. Plant Pathology 53:692-704.  

Flier WG and Turkensteen LI. 1999. Foliar aggressiveness of Phytophthora infestans in three potato growing regions in the Netherlands. European Journal of Plant Pathology 105:381-388. 

Fry WW, Goodwin SB, Dyer AT, Matuszak JM, Drenth A, Tooley PW, Sujkowski LS, Koh YH, Cohen BA, Spielman LJ, Deahl KL, Inglis DA, Sandlan KP. 1993. Historical and recent migrations of Phytophthora infestans: chronology, pathways and implications. Plant Disease 77:653-661.  

Gisi U. 2002. Chemical control of downy mildews. In: Spencer PTN, Gisi U, Lebeda A, editors. Advances in Downy Mildew Research. Dordrecht (the Netherlands): Kluwer p. 119-159.

Gisi U, Sierotzki H. 2008. Fungicide modes of action and resistance in downy mildews. European Journal of Plant Pathology 122:157-167.

Gisi U, Waldner M, Kraus N, Dubuis, PH, Sierotzki, H. 2007. Inheritance of resistance to carboxylic acid amide (CAA) fungicides in Plasmopara viticola. Plant Pathology 56:199-208.

Gobbin D, Rumbou A, Gessler C. 2007. Epidemiology and population genetics of grape vine downy mildew. In: Lebeda A, Spencer-Philips P, editors. Advances in Downy Mildew Research Vol. 3. Olomouc (Czech Republic): Olomouc and Palacky University. p. 205-209.

Goodwin SB, Smart CD, Sandrock, RW, Deahl KL, Punja ZK, Fry WE. 1998. Genetic changes within populations of Phytophthora infestans in the United States and Canada during 1994-96: role of migration and recombination. Phytopathology 88:939-949.

Knapova G, Gisi, U. 2002. Phenotypic and genotypic structure of Phytophthora infestanspopulations on potato and tomato in France and Switzerland. Plant Pathology 51:641-653.

Lees AK, Wattier R, Shaw DS, Sullivan L, Willain NA, Cooke DEL. 2006. Novel microsatellite markers for the analysis of Phytophthora infestans populations. Plant Pathology 55:311-319.

Sozzi D, Schwinn FJ, Gisi U. 1992. Determination of the sensitivity of Phytophthora infestans to phenylamides: a leaf disc method.  EPPO Bulletin 22(2):306-309.


Dr. Stefano Torriani 

Syngenta Crop Protection AG