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Update on Antimicrobial Research

Update on Antimicrobial Research. Prepared for Florida Citrus Industry Annual Conference Bonita Springs, FL June 12, 2014. Requirements for Management. Slow spread of disease – CHMA and insect control Treat existing infected trees Protect new plantings

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Update on Antimicrobial Research

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  1. Update on Antimicrobial Research Prepared for Florida Citrus Industry Annual Conference Bonita Springs, FL June 12, 2014

  2. Requirements for Management • Slow spread of disease – CHMA and insect control • Treat existing infected trees • Protect new plantings • Provide long-term sustainable genetic and biological solutions www.citrusrdf.org

  3. Requirements for Management • ✔ Slow spread of disease – CHMA and psyllid control • Stewardship of existing products • Label expansions • Bee health - coordination • New insect control actives www.citrusrdf.org

  4. Requirements for Management • Treat existing infected trees • Enhanced nutritionals • Plant growth regulators • Naturally occurring microbes • Thermal therapy • Antibacterial compounds www.citrusrdf.org

  5. Outline • Perspective – science, business, regulatory, market aspects of current challenge • Definitions – different languages • Resources available today • What have we learned? • Pipeline of bactericides • From where will the next products come? www.citrusrdf.org

  6. Some Definitions • Antibacterial treatments • Bactericides and Pesticides • Biopesticides (Microbial and Biochemical) • Antibiotics • Use pattern, residues, tolerance or exemption • Science • evidence over opinions, assumptions explicit, bounds what is known as well as what is unknown, creates technology options www.citrusrdf.org

  7. 3 YR 6 YR 9 YR Time to Market - Present Investment Vector Pathogen Host Probability Time www.citrusrdf.org

  8. Bactericides for Crops • To our knowledge in all of US there are only three bactericides approved for use on food crops (excluding copper); Oxytetracycline, Streptomycin and Kasugamycin • This problem is much bigger than citrus but it is ours to solve www.citrusrdf.org

  9. www.citrusrdf.org

  10. Registration of a New Active • A partial list of studies required by EPA (Additional agencies may include USDA-APHIS, FDA, CDC) • (GLN 835.1240) Soil Column Leaching and (GLN 835.2410) Photodegradation of Parent and Degradates in Soil, (GLN 835.6100) Terrestrial Field Dissipation • (GLN 835.4200) Anaerobic Soil Metabolism, (GLN 835.4100) Aerobic Soil Metabolism, (GLN 835.4300) Aerobic Aquatic Metabolism and (GLN 835.4400) Anaerobic Aquatic Metabolism • (GLN 835.2120) Hydrolysis of Parent and Degradates as a Function of pH at 25° C and (GLN 835.2240) Direct Photolysis Rate of Parent and Degradates in Water www.citrusrdf.org

  11. Registration of a New Active • Some more EPA data requirements • (GLN 850.1025) Oyster Acute Toxicity, (GLN 850.1035) Mysid Acute Toxicity, (GLN 850.1075) Saltwater Fish Acute Toxicity, (GLN 850.1075) Freshwater Fish Acute Toxicity,(GLN 850.1300) Freshwater Invertebrate Life Cycle, (GLN 850.2300) Avian Reproduction, (GLN 850.1010) Freshwater Invertebrates Acute Toxicity • (GLN 850.4100) Terrestrial Plant Toxicity – Tier 1 Seedling Emergence, (GLN 850.4150) Terrestrial Plant Toxicity – Tier 1 Vegetative Vigor, (GLN 850.4400) Aquatic Plant Toxicity – Tier 1 Vascular, (GLN 850.5400) Aquatic Plant Toxicity – Tier 1 Nonvascular www.citrusrdf.org

  12. Registration of a New Active • Further animal EPA data requirements • (GLN 850.2100) Avian Oral Toxicity, (GLN 850.2200) Avian Dietary Toxicity • (GLN 850.3020) Honeybee Acute Contact Toxicity • Human health • (GLN 870.7800) Immunotoxicity • Resistance studies with human pathogens planned for frequency of resistance determination • Other studies as directed… www.citrusrdf.org

  13. Citrus Greening Disease (Huonglongbing) SEARCH FOR AGRICULUTRAL THERAPEUTICS

  14. Biological Assays • Graft-based assay • Infected scion soaked in test solution and grafted onto uninfected rootstock, follow by PCR • Slow, low-throughput • Evidence of efficacy in planta and first look at phyto-toxicity • Open contest with InnoCentive™ promotion • Liberibacter crescens culture-based assay • Much faster, higher-throughput followed by in planta confirmation on CLas www.citrusrdf.org

  15. Prior Results • Compounds screened • ~100+ by graft graft assay and • ~400+ by culture assay • Wide variety of categories of chemicals • Antibiotics and agricultural antibiotics • Polycation polymers • Biopesticides, plant essential oils, terpenoids • New actives and non-antibiotic derivatives • Host immune modulators www.citrusrdf.org

  16. What are we looking for? • HLB treatment; effects on tree symptoms through CLas titre reduction • Sources: Solutions Page, Research, Companies • Chemical properties • MW: < 450 g/mol preferably < 250 g/mol • Log Kow: 2 to 4 • pKa: 2 to 6.5 preferably 3 to 5.5 • Volume of phloem: 10 ft tree, 1000 L • ? pH: 8.0 – 6.0 stylectomy vs fractionation www.citrusrdf.org

  17. Relationships • Looking inside the box… • Companies, facilitate turn-key screening • Looking outside the box… • Repurpose products with regulatory advantage • Failed antibiotics with good safety profiles • 25(b) minimal risk pesticides • All commercial compounds fitting our chemical profile and having existing tolerances on other food crops www.citrusrdf.org

  18. Current Testing Resources www.citrusrdf.org

  19. Requirements and Results www.citrusrdf.org

  20. www.citrusrdf.org

  21. Risk Remaining at this Stage • Technical • Commercial scale delivery, efficacy, phytotoxicity • Cost • Regulatory • Commercial Partner(s) • Market acceptance www.citrusrdf.org

  22. Build on Success–Expanding Teams • Pivot our focus – connecting corporations • Sponsored research base from CRDF and others, researchers, reviewers, public solutions • Improved communication; knowledge and data sharing between and within grower, researcher, government, corporate sectors • CRDF Board and Committees; RMC, CPDC, IRCC • Research pipeline now enhanced with government funding $21mm MAC, $25mm SCRI www.citrusrdf.org

  23. What comes next? 1. Field trials with top priority 2. Field trials with major challenges www.citrusrdf.org

  24. 3. Field trials with commercial partners 4. Development pipeline www.citrusrdf.org

  25. Acknowledgements: Bob Shatters, USDA-Ft. Pierce, FL Ed Stover, USDA-Ft. Pierce, FL Chuck Powell, UF-Ft. Pierce, FL Ping Duan, USDA-Ft. Pierce, FL Muqing Zhang, UF-Ft. Pierce, FL Eric Triplett, UF-Gainesville, FL BrijMoudgil, UF-Gainesville, FL Parvesh Sharma, UF-Gainesville, FL Nian Wang, UF-Lake Alfred, FL Claudio Gonzalez, UF-Gainesville, FL Mark Nelson, Echelon Corp. Jim Dukowitz, Technology Innovation Group Harold Browning, Jim Syvertsen, CRDF

  26. Contact: catp@citrusrdf.org solutions@citrusrdf.org tom.turpen@innovationmatters.com Thank-you

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