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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 What people really want out of science are ... – PowerPoint PPT presentation

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Title: Update on Antimicrobial Research

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

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

Requirements for Management
  • ? Slow spread of disease CHMA and psyllid
  • Stewardship of existing products
  • Label expansions
  • Bee health - coordination
  • New insect control actives

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

  • 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?

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

Time to Market - Present Investment
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

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Registration of a New Active
  • A partial list of studies required by EPA
  • (Additional agencies may include USDA-APHIS, FDA,
  • (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

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

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

  • Citrus Greening Disease (Huonglongbing)

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
  • Open contest with InnoCentive promotion
  • Liberibacter crescens culture-based assay
  • Much faster, higher-throughput followed by in
    planta confirmation on CLas

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

What are we looking for?
  • HLB treatment effects on tree symptoms through
    CLas titre reduction
  • Sources Solutions Page, Research, Companies
  • Chemical properties
  • MW lt 450 g/mol preferably lt 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

  • 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

Current Testing Resources
Requirements and Results
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Risk Remaining at this Stage
  • Technical
  • Commercial scale delivery, efficacy,
  • Cost
  • Regulatory
  • Commercial Partner(s)
  • Market acceptance

Build on SuccessExpanding 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

What comes next?
1. Field trials with top priority
Category of Compounds Description Partner
Antibiotics Oxytetracycline Streptomycin (Kasugamycin?) Commercial
GRAS-like Plant Essential Oils Natural Products cymene, carvacrol, etc. CRDF-sponsored formulation research
2. Field trials with major challenges
Category of Compounds Description Partner
Agricultural Antibiotics Zhongshengmycin Validoxylamine A Source? - Research
3. Field trials with commercial partners
Category of Compounds Description Partner
Biopesticides Surfactin (lipopetides) Company C
Host Immune Modifiers One marketed compound One pipeline compound Company C
4. Development pipeline
Category of Compounds Description Partner
Polycation polymers Proprietary biodegradable polymers Company D
Bacterial protein target LdtR (Gonzalez) Lead refinement Highly active, no human homolog, transcription regulator, essential role in cell wall remodeling Company D
Bacterial protein target SecA (Wang) Lead refinement Highly active, no human homolog, protein secretion, essential role in effector secretion Company D
Non-antibiotic derivatives Tetracycline derivatives Company E
  • 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
  • Brij Moudgil, 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

  • Contact
  • catp_at_citrusrdf.org
  • solutions_at_citrusrdf.org
  • tom.turpen_at_innovationmatters.com
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