How resistant is Northern Europe? Fredericia August 18, 2011 Hans 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-site Metabolic Target enzym mutation / binding increased metabolic activity Qualitative (practical): yes/no Mode of action Quantitative: decreasing efficacy Resistant individuals practically completely resistant Varying degrees of resistance Weeds: “nests” in field Gradual shift of whole populations Fitness good Other MoA works dominant heredity chemical structure/ mechanism of degradation 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 Resistance to sulfonylurea and triazolopyrimidine Proline 197 to Ile, Ala, His - Raphanus Resistance to imidazolinone Alanine 122 to Thr - Xanthium Ser 653 to Thr - Amaranthus spp. Resistance to sulfonylureas Proline 197 to Arg,Gln,Ser - Kochia, Papaver Resistance to all ALS Inhibitors Proline 197 to Leu - Amaranthus spp. Alanine 205 to Val - Xanthium Resistance to SU + IMI + TP Trp 574 to Leu - Sisymbrium, Ambrosia The ALS enzyme show its major mutations on the following amino acids: ALA 122, PRO 197, ALA 205, TRP 574, SER 653 Metabolic Resistance ALOMY schematic illustration of its development (UK, D) % individuals/ population metsulfuron tribenuron thifensulfuron amidosulfuron FOP‘s 9 g/ha mesosulfuron . . flurpyrsulfuron mesosulfuron 15 g/ha propoxycarbazone . Ureas . P450 Potenz 0 6-8 8-12 today years 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 OP-Ester Pyrethroide Häutungsbeschleuniger Oxadiazine Neonicotinoide Diamide Metamorphosehemmer Example monitoring: Blumeria graminis/proquinazid Routine monitoring since 2006 Characterisation of less sensitive isolates with full dose response Cross-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 Example: Methodology development for monitoring M. aeneus adults susceptibility to indoxacarb Vial test BTL (a) pooter (b) roller mixer (c) glass tube a b These are the proper glass vials used for 2008 – 2009 bioassays c International survey resistant weeds Characterization of Herbicide resistant Weeds Example: Evaluation Methods at the whole plant level • Greenhouse test on pots : Harvest Seeds or Plants Planting seeds or transplanting plants From seeds 15 days are need to reach stage 2-3leaves Evaluation at 21 DAT Plants at 3 leaves GS Control Resistant Growth and Evaluation Susceptible Treatment Greenhouse set up 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 weed 1. - crop rotation: only winter or summer crops, • 2. - reduced/one-sided agricultural means: • 3. 2. No plough, very early seeding times - allow/accept imperfect efficacy: many new seeds One-sided application of herbicides 1. 2. 3. 4. 3. Best for grasses: only wi-cereals - 1 mode-of-action solo - only post-em spring - no change (MoA) in the whole crop rotation - no mechanical or other field hygene 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 – – – Winter cereals mono culture Only product registered for several years: Ralon (fenoxaprop-e) ACCase target-site (and metabolic) resistance problems • APESV in Sweden • 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?) Resistance to ALS Inhibitor Herbicides ALS Target Site Mutation: Stellaria media case Years 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 Crops Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Spring Barley Herbicide Treatments Chlorsulfuron + HBN Chlorsulfuron + HBN Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl + MCPP Metsulfuron-methyl Metsulfuron-methyl Confirmed resistance Two important characteristics for the development of herbicide resistance were put together in this field : crop monoculture and use of the same herbicide (9 years of sulfonylurea treatments (chlorsulfuron and metsulfuron-methyl)). Population metsulfuron-methyl sulfosulfuron tribenuron-methyl flupyrsulfuron-methyl florasulam fluroxypyr bentazone Ref S S S S S S S A R R R R S S S B R R R R S S S C R R R R R S S D R R R R R S S E R R R R R S S F R R R R S S S 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 positive negative Relatively broad spectrum of MoA classes available Not in Nordic No 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., ACCaseInh. Changes in agronomic practices can lead to favour specific weed species 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) – Glyphosate/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? Thank you for your attention Das DuPont Oval, DuPont™, The miracles of science™ und alle mit ® gekennzeichneten Produkte sind für E.I. du Pont de Nemours and Company oder eine ihrer Konzerngesellschaften markenrechtlich geschützt. Copyright © 2010 E.I. du Pont de Nemours and Company. All rights reserved.