Source: 3BAR BIOLOGICS INC. submitted to
APPLICATION OF PSEUDOMONAS SPP. FOR BIOCONTROL OF PLANT DISEASES IN HYDROPONIC SYSTEMS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1025836
Grant No.
2021-33530-34505
Cumulative Award Amt.
$100,000.00
Proposal No.
2021-01152
Multistate No.
(N/A)
Project Start Date
Jul 1, 2021
Project End Date
Feb 28, 2022
Grant Year
2021
Program Code
[8.2]- Plant Production and Protection-Biology
Recipient Organization
3BAR BIOLOGICS INC.
4887 CHADDINGTON DR
DUBLIN,OH 43017
Performing Department
(N/A)
Non Technical Summary
Crazy Root disease (Agrobacterium rhizogenes; CR) has recently been recognized as an emerging disease, particularly in greenhouse hydroponic tomato production. There is currently no commercial product for control of CR disease. Consequently, growers must sterilize or throw away all infected materials leading to added expenses and operational downtime. Use of biocontrol in greenhouses continues to increase; however, a significant problem in the expanding biologicals market is inconsistent performance of biological products. 3Bar Biologics is bringing to market a novel beneficial microbe delivery system, to improve suboptimal, inconsistent performance of biological products. The delivery system is easily activated on-site by the grower, by simply pushing a button to combine the stabilized bacteria inoculum with the liquid growth medium. 3Bar's disposable bioreactor technology opens up the potential for growers to apply more effective microbial strains with CR control capability. Discovery research at The Ohio State University has identified several Pseudomonas strains capable of CR control. The Phase I project aims to prove feasibility to prevent CR disease in hydroponic tomato production using the identified Pseudomonas strains delivered with 3Bar's system. The proposed work addresses three technical objectives: i) maximize cellular yields in the system with identified Pseudomonas strains, ii) characterize compatibility of new formulations for feasible use in hydroponics systems, and iii) evaluate efficacy in greenhouse hydroponic tomato production. The ultimate goal is to develop a broad-spectrum biocontrol product for use against multiple plant diseases, particularly Crazy Root and fungal root rots, and at the same time provide "probiotic" benefits to plants to increase vegetable yield and quality in hydroponic systems. The proposed project is directly aligned with USDA NIFA Challenge Area 1) Global Food Security, and Priority 8.2.3) to research bio-based approaches for plant protection against abiotic and biotic stresses.
Animal Health Component
50%
Research Effort Categories
Basic
0%
Applied
50%
Developmental
50%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2151460106060%
2031460106040%
Goals / Objectives
The ultimate goal of the project is to develop a broad-spectrum biocontrol product for use against multiple recurrent diseases in hydroponic vegetable production systems. Common diseases of hydroponic systems include Crazy Root disease (Agrobacterium rhizogenes), fungal root rots (caused by Pythium, Fusarium, and Phytophthora spp.), and diseases of the leaves (Powdery Mildew; Oidium lycopersicum) and fruits (Gray Mold; Botrytis cinerea). Most methods for disease control involve routine use of chemical pesticides and sterilization agents; however, the hydroponic vegetable production industry is beginning to shift its focus toward the use of biocontrol agents that limit the spread of diseases, are safer for workers and consumers, and are easily produced and applied. Currently, there are few effective biocontrol-based products available to control diseases on hydroponically produced vegetables. To meet this overall goal, application of Pseudomonas spp. will be used for control of plant diseases in hydroponic systems. Pseudomonads (Pseudomonas spp.) have been widely studied for their biocontrol activity against numerous plant pathogens (including, most notably Pythium spp. and Phythopthora spp.), are excellent root colonizers, and can sometimes exhibit plant growth promoting activity. Despite the significant body of research on the benefits of Pseudomonas spp. over the past 30 years, very little successful commercialization has occurred due to the lack of effective formulation and delivery technologies for these and other gram-negative, non-spore forming microbes. To address this issue with commercialization of pseudomonads and other non-spore forming beneficial bacteria, 3Bar Biologics developed and patented (US 10,774,298) a novel beneficial microbe delivery system for improving microbial product viability in the supply chain.Using target Pseudomonas spp. strains and 3Bar's beneficial microbe delivery system, the specific goals of the Phase I project include:1) Maximize cellular yields of the solid and liquid phases of the delivery system. Technical objectives to meet this goal include: i) development of freeze-dried formulations of each target strain stable at room temperature for at least 6 months, ii) improved delivery system design including gas permeability, liquid volumes, and amount and type of growth media for increasing bacterial cellular yields, and iii) evaluation of growing bacteria consortium in the delivery system. Efforts will result in a second-generation delivery system for hydroponic use with improved growth performance for target strains or combined consortia.2) Characterize the stability and compatibility of new formulations for feasible use in hydroponic systems. Working directly with industry partners to understand hydroponic system operation and common chemical products used (e.g., nutrient solutions), the technical objective is to develop a chemical compatibility chart for nutrient solutions and other products that are compatible with the bacteria strains and fits grower practice.3) Evaluate efficacy in tomato hydroponics trials on Crazy Root disease. The technical objectives to meet this goal involvetesting in OSU's pilot-scale hydroponics system i) individual strains under direct disease pressure, ii) combinations of strains (consortia) for synergistic effects to determine efficacy, and iii) individual strains for yield improvement (no pathogen pressure). All efficacy trialswill be conducted using the candidate formulations and delivery system. Resulting efficacy data will support the feasibility to select Pseudomonas strains for further development of a biopesticide to control Crazy Root disease, with the intent in Phase II to expand development for control of fungal root rot diseases.
Project Methods
Methods for each goal/objective and project task. Objective 1: Maximize cellular yields of the solid and liquid phases of the delivery system. Task 1: Develop dry formulation of Pseudomonas spp. strains. Building upon previous efforts, lead candidate formulations will be developed for the target strains of Pseudomonas (e.g., 1B1, 93G8, and 48G9). Current commercial practice involves freeze drying gram-negative bacteria. Key design variables appropriate for formulation include consideration of the culture medium (e.g., nutrient composition, conditioning additives), growth stage when the culture is harvested, and additive type and amount (e.g., lyoprotectant) in formulation. Completion of this task will result in dry formulations for each of the target strains. Task 2: Develop improved delivery system design. The following experiments will be used to improve upon the current MVP design with the goal of increasing cellular yields by at least 10-fold in the liquid phase and extend the window of use beyond 28 days.Experiment 1: Delivery system design and size. The next generation prototype utilizes single-use polyethylene bags ("bladders") and is being redesigned to improve performance for production scale-up and automated manufacturing. Gamma-irradiated polyethylene bags commonly used in food packaging are low-cost, available through multiple suppliers, and in a range of film thicknesses, gas permeability properties, and sizes (1 L to 1000 L). The experiment aims to evaluate different film thicknesses, gas permeability properties, liquid volumes and headspaces to see if the cellular yields can be increased and maintained for 90 days or longer after activation.Experiment 2: Amount and type of growth media. This experiment will evaluate the amount and type of growth media to increase cellular yields in the delivery system. To start, tryptic soy broth (TSB; a common nutrient-rich growth media) will be autoclaved and aseptically filled into sterile bladders for testing. Bladders of different sizes (10 L, 20 L) and liquid fill volumes (50%, 75%, 90%) will be evaluated with different nutrient strengths (10%, 50%, and 100% TSB) to determine the impact of head space and nutrient strength on cellular yields. Additionally, other nutrient growth medias will be identified and efforts to evaluate initiated to determine the feasibility of increasing cellular yields while minimizing material costs associated with media. Experiment 3: Evaluate a consortium of beneficial microorganisms in the delivery system. The purpose of this task is to evaluate the utility of the delivery system to deliver not only a single strain of Pseudomonas but also a consortium of known beneficial microorganisms. To do so, we will evaluate combinations of the three target Pseudomonas strains (1B1, 93G8, 48G9) in the same bioreactor system. The dry formulated microbes will be added together in different combinations, inserted into the cap, and attached to the main delivery system according to current manufacturing practice.All tests for Experiments 1, 2, and 3 will include three different strains of Pseudomonas (1B1, 93G8, and 48G9). Delivery systems will be activated and sampled at 1, 2, 7, 14, 21, 28, 60, and 90 days post activation (DPA). Each experiment will be run twice. Viable cell counts from each sample will be determined by dilution plating and enumeration using standard microbiology techniques. Overall, growth rates and cellular yields (both individually and through co-culturing) of activated delivery systems will be determined. The completion of this task will result in a second-generation delivery system for hydroponic use with improved growth performance for target strains, either select single strains or combined consortia.Objective 2: Characterize the compatibility of new formulations for use in hydroponic systemsTask 3: Evaluate compatibility of strains with nutrient solutions (fertilizers) and other products applied within recirculation system. 3Bar will work directly with Village Farms to understand hydroponic system operation and common chemical products used by the industry requiring compatibility with the beneficial microbes. Some nutrient solutions contain micronutrients (such as copper, a known biocide) that may be detrimental to the bacteria. Samples of bacterial cultures will be loaded into 96-well plates and exposed to different organic and inorganic nutrient solutions commonly used in the industry. To do so, 100µL of test solution will be serially diluted in 2-fold increments from 1X to 1/8X of the recommended concentration. To these, an equal volume of bacterial culture will be added. Plates will be incubated at room temperature for 24 hr, after which viable cell counts from each sample will be determined by dilution plating and enumeration using standard microbiology techniques. Completion of this task will allow for the development of a chemical compatibility chart for nutrient solutions and other products with a range of active ingredients. Objective 3: Evaluate efficacy in hydroponic trials.Task 4: Conduct trials of new formulations in a hydroponic system. We will further test the strains using 3Bar Biologics' second-generation delivery system. Our initial test will be in three parts: 1) testing individual strains under direct disease pressure in pilot scale hydroponic units in the Taylor laboratory using bacteria grown in 3Bar Biologic's delivery system, and 2) testing a combination of strains (consortia) to determine their efficacy in controlling CR, and 3) testing individual strains for yield improvement (no pathogen pressure). Experiment 1: Pilot scale testing of strains. The sterilizable test system allows direct application of microbes and pathogens under actual hydroponic conditions. The infection process was optimized with A. rhizogenes and can achieve nearly 95% disease efficiency. Each tray will be pretreated with the test Pseudomonas strains (individually or in combination) grown in 3Bar Biologic's delivery system. Two-week-old plants grown in oasis cubes or soilless media will be placed in the individual rockwool cubes. Plants will then be treated with an adequate dose of A. rhizogenes to ensure disease at 6, 12, 24, 48 and 72 hours after treatment. Plants will be examined for the presence of CR and the efficacy of treatment determined. Several controls will be utilized, including mock inoculated, non-treated, and a non-disease causing variant (i.e. cured) strain of A. rhizogenes. All trials will be done with four replicates (4-tables) and repeated three times. Experiment 2: Combination testing of strains for synergistic effects. To further examine the potential of Pseudomonas to inhibit CR disease, combinations of Pseudomonas will be tested to determine if there is any improvement in pathogen control above single strain application. Double and triple combinations will be tested to determine if there is any change in biocontrol activity.Experiment 3: Yield testing. Yield testing will be conducted using Pseudomonas grown in 3Bar's delivery system with application for growth promotion potential in the absence of any disease pressure. Yield testing will be conducted using Bato BucketTM system used for growing vine tomatoes for fruit production. Tomato plants (var. Rebelski -F1) will be germinated in rock wool cubes and transferred to the individual Bato Buckets and inoculated with Pseudomonas. We will initially apply Pseudomonas once every month to the root system of the plant. Plants will be measured for shoot height and leaf surface area. Plants will be trellised and allowed to produce fruit for three months. Ripe fruit will be harvested throughout the experiment and weighed. At the end of three months, all fruit will be harvested and weighed. We expect to be able to complete 2 additional trials over the duration of the Phase I funding.

Progress 07/01/21 to 02/28/22

Outputs
Target Audience:The target audience for the biocontrol product is hydroponic vegetable growers in North America (United States and Canada) and Europe, specifically tomato production. In just 25 years, the hydroponic greenhouse vegetable industry has grown from about 0.5% of the retail grocery sales of tomatoes, to today's market for tomatoes that is greater than 60% in retail grocery sales. In the United States, there are 14 top fresh produce greenhouse growers, whose operations total approximately 1,000 acres of production. Greenhouse tomato production is devasted annually by plant diseases resulting in losses as high as $1M per year at a single 40-acre operation. Plant diseases that can cause plant loss and/or operational downtime are especially damaging, leading to repopulation of an area that will be out of production for 12-15 weeks. Current control techniques largely involve crop sanitation procedures and removal of affected plants during crop cycles. Many labeled chemical pesticides for greenhouse tomatoes do not meet the 3 day post-harvest interval and/or are incompatible with beneficial biocontrol agents. Further, due to consumer demands for non-blemished fruit, free of pesticides and other chemical residues alternative methods for plant disease control is essential. To this end, the industry is increasingly turning to bio-based solutions to control pests and diseases. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?On a regular basis, 3Bar Biologics employs 3-4undergraduate students as student interns, who work part time while going to school and full-time during the summer. Students learn basic microbiology skills, including aseptic technique, plating and enumeration, creating media, etc, and lead a project during the summer that supports 3Bar's technology development goals. 3Bar Biologics works with the Tech Ohio Diversity and Inclusion internship program to hire student interns. The program provides college students with hands-on experience in some of Ohio's most innovative companies, while providing startup tech companieswith great talent to help them grow. 3Bar hihgly values the student intern program as we gain exceptional support from the students, while contributing to bioeconomy workforce development. How have the results been disseminated to communities of interest?Ohio Controlled Environment Agriculture Center (OCEAC)is hosting the first annual symposium in conjunction with the Cultivate 2022 horticulture trade show (held each year in Columbus, Ohio) onJuly 20, 2022, "Advancement of Microbial Technologies for Controlled Environment Agriculture". 3Bar Biologics will be presenting on the collaborative work with The Ohio State University to develop a Pseudomonas biocontrol product for hydroponic production systems partially funded under this SBIR Phase I effort. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The key outcomes for each objective include: 1)Maximize cellular yields of the solid and liquid phases of the delivery system. i) Development of freeze-dried formulations of each target strain stable at room temperature for at least 6 months. Initial formulation efforts involved freeze-drying Pseudomonas strains using the baseline formulation of 10% sucrose + 10% skim milk. Baseline freeze-dried formulations of each strain were created and stored at 22oC and 30oC in high-barrier plastic conical vials in a storage container with dessicant and evaluated for stability with time. 1B1 and 93G8 demonstrated similar stability at both temperatures;while 48G9 declined more rapidly, particularly at higher temperature. Based on the determined decay rates, both 1B1 and 93G8 achieved the 1-year goal for shelf-life. Due to the poor stability of 48G9, it was removed from further formulation efforts.Liquid cultures were centrifuged and concentrated to either 2X, 5X, or 20X, then formulated with 10% sucrose + 10% skim milk as the baseline formulation. Freeze-dried powders were stored at 22oCand sampled at various time points.Concentrating the liquid culture 20X or greater was foundimportant for maximizing initial cell loading and extending shelf life. ii) Improved delivery system design including gas permeability, liquid volumes, and amount and type of growth media for increasing bacterial cellular yields. 3Bar Biologics continues to advance its delivery system through evaluation of different packaging materials and system design. Polyethylene bags commonly used in food packaging are low cost, available through multiple suppliers, and in a range of film thicknesses, gas permeability properties, and sizes (1 L to 1,000L). The liquid volume and bag total capacity were varied to evaluate the impact of associated headspace and gas permeability due to different surface area-to-volume (SA:V) ratios. Growth kinetics of 1B1 in the delivery system varied due to the different SA:V ratios,where the highest cell concentration was achieved with the greatest SA:V (108.6 m-1) and the lowest with the least SA:V (34.2 m-1). However, after approximately 30 days post activation, the cell viability at the highest SA:V began to decline more readily compared to the other lower SA:V systems.The type and amount of nutrient media can impact cellular yields in the delivery system. Growth kinetics of 1B1 and 93G8 were evaluated using tryptic soy broth (TSB; a common complex, nutrient-rich growth media) at different nutrient strengths (10%, 50%, and 100%). Both 1B1 and 93G8 grow quickly to >108 CFU/mL within 24 hours and continue to grow to approximately 109 CFU/mL by four days post activation. When the fermentation is not nutrient limited (TSB concentrations 50% and greater), the cells maintain viability >108 CFU/mL for 60 days before starting to decline. iii) Evaluation of growing bacteria consortium in the delivery system. Co-fermentation of multiple strains in the delivery system is desired, with the intent that suitably high concentrations of each strain can be achieved along with maintaining or improving efficacy. To start, both Pseudomonas spp. 1B1 and 93G8 were grown together in the delivery system. To differentiate cell counts, total viable cells were determined using TSA and 1B1 cell counts were differentiated using TSA amended with chloramphenicol (an antibiotic 1B1 is resistant to). The differences in total and 1B1 differentiated cell counts were used as an approximation for 93G8. While both strains can be co-fermented in the delivery system, 93G8 appears to be more dominate in growth. 2) Characterize the stability and compatibility of new formulations for feasible use in hydroponic systems. Elite Pseudomonas spp. were evaluated for compatibilitywith nutrient solutions commonly used in hydroponic growing systems. Specifically, the nutrient solution used in the efficacy trials (KNo3(2 parts): CaNO3(5 parts): Vine fertilizer (6.5 parts)) was evaluated. No negative impacts of the nutrient solution on thePseudomonasspp. were observed. 3)Evaluate efficacy in tomato hydroponics trials on Crazy Root disease. i) Individual strains under direct disease pressure. Pseudomonas strains 1B1, 93G8, and 48G9 were grown utilizing normal laboratory protocols (i.e., grown in 50 mL LB in a flask on an orbital shaker overnight at 28oC followed by cell collection via centrifugation and resuspension in water to an OD600nm=1) or utilizing 3Bar Biologics' delivery system (i.e., following the protocol that came with the system) and tested under hydroponic conditions.Tomato (cv. MoneyMaker) seeds were germinated and grown in 1" rockwool cube and grown for 6-8 weeks prior to experiment initiation. Hydroponic solution was added once a week as fertilizer to the young seedlings upon germination. Young tomato plants were treated withPseudomonas(lab or delivery systemgrown). Treated plants were transferred to a plastic bag for 6 hours before A. rhizogenes was added to the roots and allowed to soak for an additional 3 minutes. The inoculated plants were transplanted to rockwool blocks (4"x4"x4") (Grodan®, Milton, ON) and grown under hydroponic conditions. Plants were visually evaluated after 4-6 weeks for disease incidence. Results from the biocontrol trials are promising.The disease incidence of the A. rhizogenes treated control was above 80%. Plants treated with lab grown elite biocontrol strains 1B1 or 93G8 exhibited disease incidence of 23 and 25%, respectively. Plants treated with strains 1B1 and 93G8 produced in the deliverysystem exhibited disease incidence of 20 and 23%, respectively. There are no significant differences in activity observed between bacteria that are produced under laboratory conditions versus those that are grown utilizing the deliverysystem indicating the validity of using the deliverysystem to produce a viable product. Further work with 48G9 is being halted given its lower efficacy. ii) Combinations of strains (consortia) for synergistic effects to determine efficacy. Several combinations of Pseudomonas spp. were evaluated in the biocontrol trial. A double combination (1B1 + 93G8) and a triple combination (1B1 + 93G8 + 48G9) were tested using bacteria fermented individually in the delviery system, then combined in equal parts and applied to the tomato plantlets during transplanting. Interestingly, intermediate results of disease incidence were observed for both the double (37.5%) and triple (33%) combinations. Results from the combination experiment indicate, that although better than untreated control, the combination results were less active in preventing disease than the treatments that utilize single strains of Pseudomonas (either 1B1 or 93G8). Future work will be needed to determine why combination of strains are less active than when used individually, but will not affect product development since these strains will likely be produced and sold separately. iii) Individual strains for yield improvement (no pathogen pressure).Laboratory grown Pseudomonas strains 1B1 and 93G8 were previously shown to have no impact on tomato yield when grown in the absence of A. rhizogenes and could help reduce yield losses when A. rhizogenes was present. Tests were conducted to determine if there were any deleterious effects to tomato yield when microorganisms produced utilizing the delivery system are used as inoculum and no disease pressure is present.The average total number of fruits on water-treated (blank) plants was 14.8 fruits per plant. Plants pretreated with a single dose of 1B1 or 93G8 produced 14.8 and 14.1 fruits per plant, respectively. A. rhizogenes treated plants (alone) produced 6.8 fruits per plant. There were no differences in terms of average individual fruit weight or fruit diameterfor fruit across all treatments. Similar to laboratory grown conditions, no deleterious effects to tomato yield were found when microorganisms produced utilizing the delivery system.

Publications

  • Type: Theses/Dissertations Status: Published Year Published: 2021 Citation: Cecilia Chagas de Freitas. 2021. Biology and Management of Agrobacterium rhizogenes. The Ohio State University, Department of Plant Pathology.