Source: VIRGINIA POLYTECHNIC INSTITUTE submitted to NRP
EVALUATION AND INVESTIGATION OF BIOLOGICAL CONTROL AGENTS AGAINST CROWN GALL OF GRAPE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1019545
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
May 9, 2019
Project End Date
Apr 25, 2024
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
VIRGINIA POLYTECHNIC INSTITUTE
(N/A)
BLACKSBURG,VA 24061
Performing Department
Alson H. Smith, Jr. Agri Res & Ext Ctr
Non Technical Summary
Crown gall of grape is a very common disease of grapevines around the world. Symptoms are the formation of galls on the trunk or other parts of grapevines. When the vines are infected, the vascular system can be compromised due to the gall formation, thus, the infected vine can be killed from the disease. The pathogen of grapevine crown gall is a bacterium Rhizobium vitis. This pathogen causes systemic infection, thus, once the vine is infected, the only true remedy is the removal of the infected vine.Unfortunately, we do not have goodmeans of managing grapevine crown gall. The best practice is a hilling of the graft union of the vine where tissues are susceptible to the infection; however, it is cost prohibitive since you have to protect the graft union with the soil in the fall, and then remove the soil in the spring (otherwise it will negatively affect the vine).I launched an international collaborative project with Dr. Kawaguchi in National Food and Agricultural Research Organization in Japan and Kumiai Chemical in Japan to address this economically important disease. The aim of this project is the validation of a biological control agent Rhizobium vitis strain ARK-1. The preliminary results indicate a very good efficacy of ARK-1 against several R. vitis isolates from Virginia.The objectives of this project are to 1)investigatea practical method to apply ARK-1 in the field, and 2) find a potential biological agent(s) that can be applied by itself or with ARK-1 to enhance the efficacy. We will conduct a series of lab, greenhouse, and field assays to achieve these objectives.
Animal Health Component
70%
Research Effort Categories
Basic
10%
Applied
70%
Developmental
20%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
21211311100100%
Knowledge Area
212 - Pathogens and Nematodes Affecting Plants;

Subject Of Investigation
1131 - Wine grapes;

Field Of Science
1100 - Bacteriology;
Goals / Objectives
Crown gall of grape, caused by Rhizobium (=Agrobacterium) vitisis a chronic and very common issue among Virginia vineyards. Galls are water and nutrient sinks that weaken plants and can eventually lead to vine death. Hypertrophic cell growth forms galls at wounds on the roots or trunk of the grapevine (Vitis spp.). Wounds can result from a variety of causes, but winter injury or mechanical damage, such as graftingare primary causes. Rhizobium vitis causes crown gall by transferring the T-DNA region of the tumor-inducing bacterial plasmid (Ti-plasmid) to the host cell, which subsequently integrates into the plant host genome.The pathogen causes a systemic infection; consequently, the only true remedy is the removal of infected vines.Currently, cultural management strategies, such as hilling of the graft union during the winter, are the predominant methods used for control of crown gall. However, many of these strategies are not feasible or sustainable due to their cost and labor requirement.I collaborate with Dr. Kawaguchiat Okayama Prefecture Agricultural Research Center in Okayama, Japan, and Kumiai Chemical in Tokyo Japan to validate a biological control agent which is anR. vitis isolateARK-1. Our preliminary results showed that ARK-1 inhibits the production of galls when both tumorigenic (= can cause galls) and ARK-1 (non-tumorigenic) are co-inoculated. ARK-1 might interfere with the pathogenic isolates by disturbing several of the tumor-causing genes.I will conduct a series of lab, greenhouse, and field studies to determine whether ARK-1 can be practically and effectively used to mitigate crown gall. We will also investigate other potential biological control agents, and develop better detection/diagnostics methods.
Project Methods
Objective 1a) Evaluate application methods, and timing of application of ARK-1 in the greenhouse and field using a pre-release, commercial product: ARK-1 biocontrol efficacy assays in tomato. Tomato seedlings will be grown from seed for two weeks in a greenhouse. Bacterial inocula will be prepared by inoculating 5 ml of YEM broth in a 15 ml culture tube with a R. vitis colony. After 48 hours on a shaker at 25C, optical densities of cell cultures will be measured at 600 nm (OD600) and adjusted to OD600 of 0.1 (~ 108 cell/ml).Four inoculation methods (Stab, Paint, Soil application, and root dip), summarized in Table 2, will be used to examine the efficacy of inoculation methods to control a mixture of four tumorigenic R. vitis isolates. If it is not noted, the cell concentration to be used in the experiments is 5 x 105 cell/mL. We will determine the best timing of ARK-1 application for each inoculation method, and then compare the efficacy of these methods.Gall formation will be recorded and galls will be measured at their widest diameter using a digital caliper at 42 days post-inoculation. For each experiment, experimental unit will be a tomato seedling. There will be five stab wounds per plant, three internal replications (= plants) and at least three experimental runs.In planta ARK-1 efficacy assays in grapevine. Similar experiments will be conducted with Vitis vinifera cv. 'Cabernet Sauvignon' and 'Chardonnay' seedlings grown from seeds collected at AHS AREC. Unless tomato experiments result in very poor outcomes, all experiments described above will be repeated with grape seedlings. I also have been in contact with two nurseries to conduct experiments at the time of propagation.Objective 1b) Determine the effect of rate of ARK-1 to reduction of crown gall: A mixture of four isolates will be prepared as described, then a dilution series will be made to create cell suspensions of 1:1, 1:2, 1:4, 1:8, and 1:10 relative ration between ARK-1 (5 x 105 cell/mL) and the four-isolate mix. The effect of the relative ratio (= treatment) will be examined using tomato and grapes using the stab method. In addition, once we identified a preferred method(s) from the objectives 1a) and 1b), other inoculation methods will be tested using different doses of tumorigenic R. vitis mix.Statistical analysis: Effects of treatments on the probability of gall formation and the average gall diameter per treatment will be analyzed using the generalized linear mixed model (GLIMMIX) or finite mixture model (FMM) in SAS (ver. 9.4, SAS, Cary, NC). The logit (assuming either the binomial (in GLIMMIX) or the zero-inflated binomial distribution (in FMM)) and the identity link function will be used for the mean probability of gall formation, and gall diameter data, respectively. Treatment factors will be considered as fixed effects and experimental run factor will be considered as a random effect. Once the effect of a fixed factor is found to be significant (P < 0.05), Fisher's Least Significant Difference (LSD, a= 0.05) will be used as a multiple comparison method.Objective 2a) Screen/sample Virginia vineyards for indigenous, non-pathogenic R. vitis strains that might have potential use as biological agents for crown gall managementIn addition to current collection of isolates, more samples from Virginia and mid-Atlantic regions will be collected. Isolation of R. vitis will be conducted on a semi-selective Roy and Sasser (RS) medium (Roy and Sasser, 1983). A modified multiplex PCR procedure (Kawaguchi et al. 2005) will be used to identify these bacterial colonies to determine whether they are 1) R. vitis or not, and if it is, 2) whether R. vitis contains a piece of DNA that causes galls or not.For isolates that are R. vitis, but do not contain Ti-plasmid, the stab co-inoculation assay with tomato and grape seedlings will be conducted. If gall formation is not observed with co-inoculation with a mixture of four Virginia isolates with grape, DNA will be sequenced to examine the similarity to R. vitis ARK-1 and other known antagonistic strains. Using the final candidates, inoculation studies will be conducted to determine the efficacy of the new candidate(s), possibility of synergistic effect with ARK-1 co-inoculation. Experimental methods will be very similar to those of objective 1 stab method. Other research topics, such as tests for antibiosis, genome comparisons to ARK-1, and gene expression study can be considered in the future.Objective 2b) Determine population diversity of the US and Japanese R. vitis isolates. DNA fingerprinting of the collected R. vitis isolates in USA (Virginia and surrounding states) and Japan will be carried out using the repetitive sequence-based (rep)- PCR (using BOXA1R, REP, REP1R-I/REP2-I primer sets, Table 3) (Kawaguchi et al. 2017; Kawaguchi and Tanina 2014), and inter-simple sequence-repeat (ISSR)-PCR methods using primer sets GTGC4, GAGC4, and GTG5.Using gel electrophoresis, amplified PCR products will be separated, and then each DNA fragment with a distinct electrophoretic mobility will be assigned a position number and a score of either 1 or 0 for the presence or absence of the fragment, respectively. In order to improve accuracy, an isolate with known fragments will be used as a control, in addition to the gel ladder, and software such as Gel Analyzer (GelAnalyzer.com) will be used. The estimation of distance between a pair of tested genes will be calculated as [1 - Dice similarity coefficient]. For calculation of Dice similarity coefficient and distance estimation, R (ver. 3.5, R Development Core Team) package "proxy" will be used. Then a dendrogram will be created using arithmetic average (UPGMA) clustering. In addition to the cluster analysis, the multiple correspondence analysis (MCA)and nominal principal component analysis (PCA) will be conducted. For MCA, the country of origin will be also used as a supplemental variable. Both MCA and PCA will be conducted in JMP Pro (ver. 14, SAS Institute, Cary, NC, USA).Objective 3) Develop a mutiplex qPCR procedure to be able to detect relative quantity of ARK-1 in the grapevineWe will modify a singleplex qPCR protocol of R. vitisto develop a multiplex real-time PCR assay targeting cytochrome oxidase (COX), the R. vitis virD2 gene (for a tumorigenic R. vitis), and contig 19 (for ARK-1).?Once the protocol is established, selected isolates will be used to determine the efficacy of the qPCR protocol. Then, with the final protocol, there will be a series of studies to be conducted to determine interaction between a tumorigenic R. vitis and ARK-1. Treatments will be 1) ARK-1, 2) a tumorigenic R. vitis, and 3) simultaneous co-inoculation of ARK-1 and the tumorigenic R.vitis. At 0, 1, 5, 15, 24, 48, and 72 hours after inoculation, the surface of seedling will be sampled (destructively), and subjected to the multiplex-qPCR procedure. Based on the outcome, the time interval will be extended. The second experiment will examine the timing of ARK-1 application. ARK-1 will be inoculated -72, -48, -24, -15, -5, -1, 0, 1, 5, 15, 24, 48, and 72 hours before a tumorigenic isolate, and samples will be examined later to compare relative cell number between ARK-1 and the tumorigenic isolate. (Note: negative time point indicates the tumorigenic isolate will be inoculated first.) The experimental settings and analysis will be similar to those described in objective 1.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:The primary audience is grape growers in Virginia and surrounding states. The audience also includes other stakeholders in the industry, including business owners, Extension agents, and chemical companies. The results of the research also have an impact on scientific society in both applied plant pathology and related fields because the causal agent of crown gall belongs to the genusRhizobium (previously known as Agrobacterium), which includes species that are important not only as plant pathogens but also as agents for genetic transformation of plants and fungal species. Changes/Problems:Although we have isolated more than 100 non-tumorigenic R. vitis strains from regional vineyards, none have yet shown an ability, like ARK-1, to protect against gall formation by Ti-inducing strains of R. vitis. We will collect more isolates from non-symptomatic vines in the future to see if the epiphytic population ofR. vitisyields better results. What opportunities for training and professional development has the project provided?Mr. Abdullah Nahiyan is pursuing his M.S. degree under my supervision. In addition, three non-student research associates have been trained to conduct experiments related to this project. How have the results been disseminated to communities of interest?Extension: Results from our studies are presented as part of an online video posted on my blog (grapepathology.org). Research: We presented our results at two regional and one national scientific meeting (see Products). What do you plan to do during the next reporting period to accomplish the goals? We showed the efficacy of ARK-1 when it was challenged with higher cell numbers of tumorigenic isolates and when it was applied at different time points relative to the inoculation of tumorigenic isolates. I believe that we have enough evidence to show that ARK-1 is a very effective biological control against tumorigenic R. vitis from the U.S. We are currently conducting a series of greenhouse experiments to determine an effective and practical means of ARK-1 application (e.g., spray, root dip, and soil drench). Once we find a suitable method, we will use formulated ARK-1 (i.e., freeze-dried product) to validate our results. In addition, I will collaborate with commercial nurseries to apply ARK-1 at the time of grafting to determine the efficacy and duration of protection. We will also conduct a study to determine the change in cell number (or relative quantity of cell) over time to understand the biology of both tumorigenicR.vitisand ARK-1 using the relative-quantitative PCR procedure developed in this project and traditional colony forming unit estimation methods. We will continue to screen R. vitis isolates from different states as potential biological control agents against grapevine crown gall.

Impacts
What was accomplished under these goals? Evaluation of the effect of timing of application (pre-and post-infection); Rhizobium vitis ARK-1 was inoculated prior to being challenged by a mixture of four tumorigenicR. vitisisolates (= pathogenic isolates) in a greenhouse study using tomato seedlings and grapevines. Hereafter this tumorigenic R. vitis mix will be referred to as a Ti-mix. The ARK-1 inoculation times tested were 0, 1, 3, 24, and 48 hours before and after TI-mix inoculation. When ARK-1 was applied at the same time as the Ti-mix (= co-inoculation), it resulted in more than 90% reduction in both gall incidence and size. When ARK-1 was applied at different time points, nearly all inoculation times resulted in a significant (P < 0.05) reduction of gall incidence and size. ARK-1 was more effective when it was applied at least 24 hours before Ti-mix inoculation, and resulted in reductions that were equivalent to that of co-inoculation. Moreover, ARK-1 application was able to significantly reduce both gall incidence and size when ARK-1 was applied within 24 hours after the Ti-mix inoculation, but after 24 hours, the reduction was not significant. Evaluation of relative ratio between ARK-1 and Ti-mix; ARK-1 applied at 5 x 10^7 cells/ml was challenged with an equal or higher cell number of Ti-mix with co-inoculation experiments. Greenhouse studies with tomato and grape plants showed that ARK-1 was able to reduce both gall incidence and size at up to five times higher cell number of the Ti-mix (= 2.5 x 10^8) cells/ml). We observed a reduction in ARK-1's efficacy as it was challenged with higher Ti-mix cell numbers. For example, ARK-1:Ti-mix ratios of 1:2 and 1:4 resulted in a 93% and 70% reduction in gall incidence, respectively. Screening for VA native non-pathogenicR. vitisstrains for potential use as biological agents; We collected symptomatic grapevines from VA, MD, OH, PA, and NY in 2018-2020. So far, we have more than 3,000R. vitisisolates isolated and identified asR. vitis. We are currently screening for non-pathogenic isolates using a multiplex PCR and plant assays. We have finished a PCR assay for species identification of R. vitis on approximately 70% of total samples. A total of 110 isolates were identified as non-pathogenicR. vitis so far. TheseR. vitisisolates, which do not possess tumor-inducing plasmid, thus, most likely do not cause disease, which is one of the characteristics of several biological control agents discovered in Japan. We are currently conducting a series of co-inoculation studies to 1) test the pathogenicity of new isolates and 2) identify potential antagonistic strains against pathogenicR. vitis using non-pathogenic isolates. Develop a qPCR procedure to be able to detect the relative quantity of ARK-1 in the grapevine The aim of this project is to develop a real-time quantitative PCR (Polymerase chain reaction) protocol that can detect the relative quantity of the subjects, which will be a mixture of grape tissue, pathogen, and ARK-1. We conducted a series of preliminary tests to set parameters for the multi-plex real-time quantitative PCR procedure (PCR primers, probes, dyes, etc.). The current procedure can simultaneously amplify and report the relative quantity of genes from grape (Cox (Cyclooxygenase) gene),R. vitis(virD2 virulence gene), ARK-1 (non-coding unique gene in a contig 19 region). In 2019 - 2020, we conducted a series of tests using grape stem tissues to develop a protocol that yields stable results.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Nita, M., Nahiyan, A. and Kawaguchi, A. (2020) 'Effect of relative cell number and timing of application of a biological control agent Rhizobium vitis ARK-1 on grapevine crown gall', Plant Health: American Phytopathological Society Annual Meeting, Online, 08/10/20
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Nahiyan, A., Mangan, A., and Nita, M. (2019) 'Biocontrol Agent Rhizobium vitis ARK-1 Reduces Grapevine Crown Gall Against Higher Cell Numbers of Tumorigenic R. vitis in a Co-Inoculation Study.', Cumberland-Shenandoah Fruit Workers Conference, Winchester, VA, 12/06/19
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Nahiyan, A., and Nita, M. (2020) 'Reduction of grapevine crown gall by co-inoculation of Rhizobium vitis ARK-1 and higher cell numbers of tumorigenic R. vitis strains', American Phytopatholotical Society Potomac Division meeting, Online, 03/12/20


Progress 05/09/19 to 09/30/19

Outputs
Target Audience:The primary audience is grape growers in Virginia and surrounding states. The audience also includes other stakeholders in the industry, including business owners, Extension agents, and chemical companies. The results of the research also have an impact on scientific society. The causal agent of crown gall belongs to the genusRhizobium (previously known as Agrobacterium), which contains species that are important not only as plant pathogens, but also as agents for genetic transformation of plants and fungal species. Changes/Problems:Due to the importation issue, we obtained a new ARK-1 product from Japan at the beginning of this project, May 2019. The shipper,Kumiai Chemical, shipped ARK-1 in late 2018, but they used an incorrect term in the importation form that caused the package to be stopped by the EPA. Thus, some of the studies were conducted using the cultured ARK-1 from the previous study. The preliminary work we had planned to do in advance of the project start date was delayed and occurred during this initial year's effort. What opportunities for training and professional development has the project provided?Graduate students and technician received training in laboratory protocols, analyses, and reporting. How have the results been disseminated to communities of interest?One journal article and one conference paper have been published. What do you plan to do during the next reporting period to accomplish the goals?I will most likely focus on the continuation of the current effort to finish the experiments we initiated in 2019. I will also start a co-inoculation study to identify more antagonistic R. vitis strains. In addition, we will start a series of greenhouse experiments to determine an effective and practical means of ARK-1 application (e.g., spray, root dip, and soil drench). Once we find a suitable method, we will use formulated ARK-1 (i.e., freeze-dried product) to validate our results. We will also conduct a study to determine the change in cell number (or relative quantity of cell) over time to understand the biology of both tumorigenicR.vitisand ARK-1.

Impacts
What was accomplished under these goals? Evaluation of the effect of timing of application (pre- and post-infection); R. vitis ARK-1 was inoculated prior to being challenged by a mixture of four tumorigenicR. vitisisolates (= pathogenic isolates) in a greenhouse study using tomato seedlings and grapevines. Hereafter this tumorigenic R. vitis mix will be referred to as a Ti-mix. The timing tested were 0, 1, 3, and 24 hours after ARK-1 inoculation. ARK-1 was only effective at 24 hours before a Ti-mix inoculation. The longer incubation time most likely allowed ARK-1 to increase its cell number. A post-infection inoculation of ARK-1 was less effective in suppressing gall incidence and gall size. We inoculated ARK-1 to tomato plants at immediate (< 5 min), 1, 2, and 3 hours after we inoculated the plants with a Ti-mix. Inoculation with ARK-1 significantly reduced the mean gall size and mean gall incidence from the treatment of a Ti-mix without ARK-1 (P£ 0.05) regardless of the timing of application. However, the reduction was less than 20% in gall incidence when ARK-1 was applied after the inoculation of a Ti-mix.On the other hand, when ARK-1 was co-inoculated with a Ti-mix, approximately 90% reduction in gall incidence was observed. Evaluation of relative ratio between ARK-1 and Ti-mix; ARK-1 was challenged with the equal or higher cell number of Ti-mix, which was co-inoculated. ARK-1 was applied at 5 x 107 cells/ml. The results from our greenhouse study using tomato plants showed ARK-1's efficacy declined when we applied a 1:4 ratio or higher. i.e., the number of ARK-1 cell is 1/4 of that of pathogenic isolates. ARK-1:Ti-mix ratios of 1:4 and 1:5 treatments resulted in significantly (P£ 0.05) larger galls than other ratios (i.e. 1:1, 1:2, and 1:3). With gall incidence, 1:1 and 1:2 ratio resulted in significantly lower gall incidence than higher ratios. We also observed an increasing trend of gall size with higher concentrations of pathogenicR. vitis. We are currently testing 1:1, 1:2, 1:3, 1:4, and 1:5 ratios using grapevines. Screening for VA native non-pathogenicR. vitisstrains for potential use as biological agents; We collected symptomatic grapevines from VA, MD, OH, PA, and NY. So far, we have a total of 242R. vitisisolates isolated and identified asR. vitis. We are currently screening for non-pathogenic isolates using a multiplex PCR and plant assays. A total of 57 isolates were identified as non-pathogenicR. vitis. I.e., theseR. vitisisolates, which do not possess tumor-inducing plasmid, thus, most likely do not cause disease. We are still processing new samples we collected in 2019. Once we complete our PCR assay, we will co-inoculate these non-pathogenic strains with pathogenic strains to see if we can identify potential antagonistic strains against pathogenicR. vitis. Develop a qPCR procedure to be able to detect the relative quantity of ARK-1 in the grapevine The aim of this project is to develop a real-time quantitative PCR (Polymerase chain reaction) protocol that can detect the relative quantity of the subjects, which will be a mixture of grape tissue, pathogen, and ARK-1. We conducted a series of preliminary tests to set parameters for the multi-plex real-time quantitative PCR procedure (PCR primers, probes, dyes, etc.). The current procedure can simultaneously amplify and report the relative quantity of genes from grape (Cox (Cyclooxygenase) gene),R. vitis(virD2 virulence gene), ARK-1 (non-coding unique gene in a contig 19 region). We are currently testing it with more samples to make sure it can produce consistent results.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Kawaguchi, A., Nita, M., Ishii, T., Watanabe, M., Noutoshi, Y., (2019) Biological control agent Rhizobium (=Agrobacterium) vitis strain ARK-1 suppresses expression of the essential and non-essential vir genes of tumorigenic R. vitis. BMC Res. Notes 12:1.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Kawaguchi, A. Nita, M. Ishii, T., Watanabe, M., and Noutoshi, Y. (2019) Biological control agent, Rhizobium (=Agrobacterium) vitis strain ARK-1 suppresses expression of the essential and non-essential vir genes of a tumorigenic R. vitis, American Phytopathological Society Annual Meeting, Cleveland, OH, 5 Aug 2019