How resistant is Northern Europe?

FredericiaAugust 18, 2011Hans G. Drobny

Resistance in Northern/Central Europe

• What is resistance?• How is it organized?• Status of resistance• How to select and to establish

resistance?• Some rules• Outlook

What is Resistance?

The naturally occuring, inheritable ability of individual biotypes within a pest population, to survive pesticide treatments which under normal circumstances would control these populations

This ability is genetically based (mutation), will be selected by the respective pesticide, and is passed onto the next generation

Characteristics of metabolic and target-site resistance

Target-siteTarget enzym mutation / binding

Qualitative (practical): yes/no

Mode of action

Resistant individuals practically completely resistant

Weeds: “nests” in field

Fitness good

Other MoA works

dominant heredity

Metabolicincreased metabolic activity

Quantitative: decreasing efficacy

chemical structure/ mechanism of degradation

Varying degrees of resistance

Gradual shift of whole populations

Fitness good

Other MoA molecules can be affected the same time

Resistance: further definitions• Cross resistance:

– A single mutation results in resistance against several a.i.‘s, mostly from the same MoA group

• Multiple Resistance– 2 or more mutations or mechanisms result in

resistance against same/different a.i.‘s or MoA groups

• Target-Site Mutations– Different locations of mutations on the enzym

can result in resistance (mostly „typical“ locations on each enzym)

– Subgroups of MoA groups can be affected in different ways: FOP/DIM, SU/TAP/IMI, strob‘s F129L

ALS Target Site Mutations

The ALS enzyme show its major mutations on the following amino acids: ALA 122, PRO 197, ALA 205, TRP 574, SER 653

Resistance to sulfonylurea and triazolopyrimidine Proline 197 to Ile, Ala, His - Raphanus

Resistance to imidazolinoneAlanine 122 to Thr - XanthiumSer 653 to Thr - Amaranthus spp.

Resistance to sulfonylureas Proline 197 to Arg,Gln,Ser - Kochia, Papaver

Resistance to all ALS InhibitorsProline 197 to Leu - Amaranthus spp.Alanine 205 to Val - Xanthium

Resistance to SU + IMI + TPTrp 574 to Leu - Sisymbrium, Ambrosia

Metabolic Resistance ALOMYschematic illustration of its development (UK, D)

P450 Potenz

0 6-8 8-12 today years

% individuals/ population

metsulfurontribenuron thifensulfuron amidosulfuron

Ureas .

FOP‘s

9 g/ha mesosulfuron .

mesosulfuron 15 g/ha .

.flurpyrsulfuronpropoxycarbazone

HRAC guide line metabolic resistance

• In cases where metabolic resistance is already present, the mode of action of the herbicide is not always the key criterion. In these cases, the mechanism of degradation can be very important and cross mode of action groups and chemistries. No classification of herbicides relating to degradation is available and such examples need to be handled on a case by case basis.

Who cares about resistance?• Industry

– RAC‘s: Resistance Action Committee – HRAC, IRAC, FRAC

• Registration authorities– Notification and precautionary

statements– Action Groups („RAG‘s“): NORBARAG

• Official and private advisors• Competition….Resistance is „sexy“!

How is resistance organized?• RAC‘s: Resistance Action

Committees– Industry representatives, global scope– HRAC, FRAC, IRAC– Public / Internet– Specialized working groups– Classification of a.i.‘s into „mode of action“

groups, and cross resistance– Guidelines for preventing/managing

resistant populations– Development of test methods– Establishment base lines

How is resistance organized -2?• RAG‘s: Resistance Action Groups

– Regulatory bodies, official advisors, industry– NORBARAG: Nordic and Baltic states– Germany: Fachausschuss PSM-Resistenz (3)– Austria: AGES „Runder Tisch Resistenz“– Monitoring resistant populations in territory– Guidelines for preventing/managing

resistant populations under local conditions– Label statements– Interface with the RAC‘s

NORBARAG Objectives• to provide a forum for information exchange

between people actively involved in research into pesticide resistance and efficacy evaluation of pesticides

• to ensure that cases of resistance in the Nordic-Baltic region is verified and listed

• to discuss strategies to avoid resistance and to manage resistant populations

• to define research needs, discuss test methodologies and agree on standards

• to promote collaboration on resistance screening and other research topics related to pesticide resistance

• to promote awareness on pesticide resistance issues e.g. by producing educational material

• to maintain contacts to similar groups in other countries

Activities of German RAG‘s

– Reports/sharing of new findings/results• Partly joint monitoring programs

– Connection to RAC‘s – local implementation– Recommendations for practical

management under German/local conditions• Crops and crop rotations• Pests• Available tools

– Fact finding for special approvals of products to manage resistance issues

– External communication via Internet

Carbamate

Oxadiazine

Diamide

Pyrethroide

Neonicotinoide

OP-Ester

Metamorphosehemmer

Häutungsbeschleuniger

Example monitoring:Blumeria graminis/proquinazid

Routine monitoring since 2006Characterisation of less sensitive isolates with full dose responseCross-resistance with metrafenone and cyflufenamid

480 airborne isolates collected in 6 European countries Study carried out by EpiLogic Regular reporting/discussion of results at FRAC working group “Azanaphthalenes” Presentation at German FRAG group

(a) pooter(b) roller mixer(c) glass tube

a

b c

Example: Methodology development for monitoring M. aeneusadults susceptibility to indoxacarb

These are the proper glass vials used for 2008 – 2009 bioassays

BTLVial test

International survey resistant weeds

Example: Evaluation Methods at the whole plant level• Greenhouse test on pots :

Characterization of Herbicide resistant Weeds

Harvest Seeds or Plants Planting seeds or transplanting plants

Greenhouse set up

Treatment

Growth and Evaluation

Plants at 3 leaves GS

From seeds 15 days are needto reach stage 2-3leaves

Evaluation at 21 DAT

Control Resistant Susceptible

Example: Results molecular genetic analysis

Mutated Allel Position 197 in bold.Mutation CCA zu ACA oder ACC : Prolin to Threonin.

Example: Resistance factor Comparison dose-response curves of sensitive reference population

(MRS) and the suspect sample (SH 1)

Resistance factor calculated from ED50-values: RF = 59,6

Relevant Weed Resistance Issues Northern Europe

• Triazin-resistant Weeds– New: Chenopodium against Metamitron

• ALOMY– Quantitative metabolic resistance against different a.i.‘s:

ureas, FOP‘s (not DIM‘s!), SU‘s, inh. of cell division– ACCase target site resistance (FOP‘s/DEN and DIM‘s)– ALS target site resistance– multiple resistances: metabolic combined with ACCase-

and ALS-target-site resistance• APESV

– Quantitative resistance against IPU and ALS-Inh.– Target-site resistance against ALS-Inh. and ACCAse-Inh.

(?)• STEME, PAPRH, MATCH, MATIN, SONAR,

CHYSE,…– Target-site resistance against ALS-Inh.– Nordic and UK; Germany: only MATSPX

Relevant Fungicide Resistance Cases Germany and Northern Europe

• Strobilurines (QoI‘s)– Target-site resistance Septoria tritici, Powdery Mildew

wheat, Erysiphe necator (grapes), Pyrenophora teres (F129L)

– NORDIC: S.tritici, M.nivale, DTR, Ramularia, P.teres• Triazoles

– „Shifting“ with several cereal diseases;– NORDIC: Septoria tritici

• Phenylamides – Downy mildew grapes and potatoes

• The „Resistance Trio“: Botrytis, Scab, Mildew– Recent reports on metrafenone/cereals/Blumeria graminis

• Special laboratory used by most organisations: Epilogic

Relevant Insecticide Resistance Cases Germany and Northern Europe

• Pyrethroides– Meligethes– Other rape pests: Ceutorhynchus, Psylloides– Colorado Potatoe Beetle– Aphids

• Carbamates and OP-Esters– Several sucking and chewing insects– Only few actives remaining

• Neonicotinoides– First reports aphids (Phorodon humili) and White flies– increasing market shares/strong exposure (start seed dressing)– X-resistant to pymetrozyn (different chemistry, IRAC group 9)– Not X-resistant to flonicamid (similar chemistry, IRAC group 9)

• Some crops with only pyrethroids (widespread resistance) and neonics: Rape, potatoes, beets

How come resistant populations?

• Naturally occurring mutations– The more individuals there are, the higher is the probability

of mutated individuals/field PLUS

• Selection of these mutants via a specific selection agent– Pesticides are powerful and mostly specific selection agents – Continuous application of the same selection agent leads to

propagation of the mutated individuals to a population • Worst case example:

– Provide optimum conditions for growth and propagation of a weed via cultural practices

PLUS– Continuous application of the same MoA herbicides– Blackgrass in the Northern German marsh areas

General Risk Faktors• Changes in agronomic pratices: favour specific

weeds – Narrow crop rotations– No-till systems

• Little (chemical) Renewal– Cost rel. to market potential

• Glyphosate/Glufosinate tolerant crops– High entry barriers (f.e. SU‘s)

• Regulatory authorities favour potentially „higher risk“ MoA classes– One-site Inhibitors (no/little side effects)– Metabolically instable (fast degradation environment)

• Cancellations/limitations „robust“ (multi-site) a.i.‘s– IPU, Trifluralin, …

• Revision 91/414/EEC into EU 1107/2009 – RAC‘s and RAG‘s do lobbying work to include/consider

resistance

Task: establishment of a resistant weed population

1. Generate high population density of target weed1. - crop rotation: only winter or summer crops,

• Best for grasses: only wi-cereals

2. - reduced/one-sided agricultural means: • No plough, very early seeding times

3. - allow/accept imperfect efficacy: many new seeds

2. One-sided application of herbicides1. - 1 mode-of-action solo2. - only post-em spring3. - no change (MoA) in the whole crop rotation4. - no mechanical or other field hygene

3. Protract seeds from affected fields to other fields

Task: establishment of a resistant weed population– it works!

• Blackgrass (ALOMY) in England– Wi-cereals, mono culture, no plough for many years– IPU/CTU (m), FOP‘s (m), DIM+FOP (t-s), Lexus®/Attribut (m und t-s), „soil

herbicides“ (m?), Atlantis (m und t-s)– Marsh areas in Schleswig-Holstein follow closely…

• Several weed species Norway– Spring cereal mono culture– Almost exclusive use of ALS-inhibitors for many years: populations of several

weed species with ALS t-s resistance : MATIN, PAPRH, STEME, SPEAR…– Other MoA groups with higher taxes– Denmark: winter and spring cereals, mixtures different MoA common: much

less problems• APESV in Sweden

– Winter cereals mono culture– Only product registered for several years: Ralon (fenoxaprop-e)– ACCase target-site (and metabolic) resistance

• APESV in Poland und CZ– WWheat mono culture– 25 years application ALS-Hemmers solo (Glean®) in autumn– Last 10 years specific ALS-inhibitors post-em spring: resistance against ALS-

inh. – last 3-5 years application FOP‘s: resistance against fenoxaprop-e (and

others?)

ALS Target Site Mutation: Stellaria media case

Resistance to ALS Inhibitor Herbicides

PopulationRef A B C D E F

metsulfuron-methyl S R R R R R Rsulfosulfuron S R R R R R R

tribenuron-methyl S R R R R R Rflupyrsulfuron-methyl S R R R R R R

florasulam S S S R R R Sfluroxypyr S S S S S S Sbentazone S S S S S S S

Years Crops Herbicide Treatments1985 Spring Barley Chlorsulfuron + HBN1986 Spring Barley Chlorsulfuron + HBN1987 Spring Barley Metsulfuron-methyl + MCPP1988 Spring Barley Metsulfuron-methyl + MCPP1989 Spring Barley Metsulfuron-methyl + MCPP1990 Spring Barley Metsulfuron-methyl + MCPP1991 Spring Barley Metsulfuron-methyl + MCPP1992 Spring Barley Metsulfuron-methyl + MCPP1993 Spring Barley Metsulfuron-methyl + MCPP1994 Spring Barley Metsulfuron-methyl + MCPP1995 Spring Barley Metsulfuron-methyl1996 Spring Barley Metsulfuron-methyl Confirmed resistance

Two important characteristics for the development of herbicide resistance were puttogether in this field : crop monoculture and use of the same herbicide (9 years ofsulf onylurea treatments (chlorsulfuron and metsulfuron-methyl)).

Cross resistant profile

Resistance ALOMY – practical findings LWA (agricultural office) Ilshofen (G.Federolf)

• Resistance against IPU: since 1993

• against Ralon S (fenoxaprop-e): 1998

• against Atlantis (mesosulfuron+iodosulfuron): 2005

• against FOP‘s (not selective in cereala): 2002

• against DIM‘s: 2007

Black Grass Management• If possible, remove occasional black-grass plants

before seeds shed, or spray off patches in June.• Avoid spreading seeds to new fields in combines,

cultivators or in straw• Place more emphasis on cultural control measures

(ploughing, crop rotation, spring cropping, delayed autumn drilling, higher cereal seed rates)

• Don’t rely solely on ‘high risk’ chemistry e.g. ‘fop’/‘dims’ (e.g. fenoxaprop) or sulfonylurea herbicides (e.g ‘Atlantis’)

• Remember that mixtures and sequences will slow, but not stop resistance development

• If resistance is suspected, have a seed or plant sample tested

Stephen Moss, Rothamsted, 2009

Risk evaluation Herbicides

Relatively broad spectrum of MoA classes available

Not in NordicNo new MoA classes in sight

Problems can be managed at individual field level

GMO political tabu

Epidemiology „controlled“:Rel. few individuals/ha+/- localized

„Ideal“ MoA classes have higher risk : ALS-Inh., ACCase-Inh.

Changes in agronomic practices can lead to favour specific weed species

positive negative

What can I do?to prevent and manage problems….

Weeds – manage by field!• Make sure no single species becomes

predominant in the crop rotation– Agronomic practices: soil tillage, seeding date, rotation– Effective use of herbicides in each season/crop

• When critical weed species becomes established– Check/change crop rotation, practices– Aim to reach levels of control as high as possible:

mixtures, sequences of herbicides; additives, optimum timing

– Intelligent rotation of a.i.‘s/MoA groups between the rotational crops

– Integrate low(er) risk MoA: „soil herbicides“ in wi-cereals, rape seed, sugar beets,…

What can I do?when chemistry is vanishing….

Diseases and pests• Hinder the outbreak of epidemics

– Crop rotation, agricultural means– Crop varieties (resistance genes)– application of fungicides/insecticides under optimal conditions ( prognosis

models, f.e. ProPlant)• Preserve available actives as much as possible

– Aim for high efficacy: use rate, additives, weather– Alternate or mix different MoA actives (include multi-site inhibitors) and

activity patterns (contact, systemic) in spray programs– Specific integration of alternative MoA products in critical (= at risk for

resistance) segments: Pyrethroides and Neonicotinoides against Pollen Beetle and Potatoe Beetle; Apple Codling Moth

News from the Chemical Industry?• Fungicides

– Several Carboxamides (Succinat-Dehydrogenase-Inh.) for horticultural and arable crops: Boscalid, Penthiopyrad (Vertisan®), Bixafen, Isopyrazam,…

– Several novel a.i.‘s against powdery and downy mildews

• Insecticides– Ryanodin-Receptor-Agonists: Diamides (IRAC Group 28)

• RYNAXYPYR®, CYAZYPYR®– ACCase-Inh.: Ketoenoles (IRAC Group 23)

• Spirotetramat

• Herbicides– Nothing new (MoA classes)– GlyphosateGlyphosate/Glufosinate (in respective GMO crops)– Multiple Tolerances: Glyphosate+ALS, +Dicamba

(GMO)

Chemical renewal selective herbicides?

• Only 2 novel MoA-classes since 1980:– ALS-inhibitors, 4-HPPD-inhibitors (triketones)– Limited market potential due to crop selectivity– Disappearance whole segments: Maize, Soya

• But the related alternative (Glyphosat tolerance) not available in Nordic/EU

– The bar is set very high by the SU‘s!• New actives from existing MoA-classes

mostly affected by both resistance mechanisms– Pyroxulam, Pinoxaden

• Registerability in EU?– Saflufenacil, Aminocyclopyrachlor, Aminopyralid

• No novel herbicidal MoA classes in sight until 2020, in the EU

ALS-inhibitors - outlook• Relevance will increase further

– Mid-term no new herbicidal groups available– New ALS-inh. enter same and new segments– Restrictions/withdrawel old herbicides (non-ALS)– Increase in generic product offerings

• Crops with modified ALS– „conventional“ breeding

• „Clearfield“: Tolerance against Imidazolinones (imazamox)

• ExpressSun®: sunflowers tolerant against Tribenuron

– GMO-crops• OptimumGAT® Stack: Glyphosate+ALS tolerance

Outlook and wishes• Consider resistance management issues when

implementing EU 1107/2009 (revision of 91/414/EEC)

• End of the GMO tabu („Eco-imperialism“)

• Fast, reliable registration and approvals of alternative actives

• Effective coordination of monitoring programs

• Effective communication and implementation of preventative programs– Who is ready/prepared to preventatively invest more

money/work?

• Plant breeding?

• Consider resistance management issues when implementing EU 1107/2009 (revision of 91/414/EEC)

• End of the GMO tabu („Eco-imperialism“)

• Fast, reliable registration and approvals of alternative actives

• Effective coordination of monitoring programs

• Effective communication and implementation of preventative programs– Who is ready/prepared to preventatively invest more

money/work?

• Plant breeding?

Thank you for your attention

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