Source: UNIVERSITY OF FLORIDA submitted to NRP
MANIPULATING CANDIDATUS LIBERIBACTER ASIATICUS MOVEMENT IN THE PSYLLIDS AND THE PLANTS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1012464
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Apr 3, 2017
Project End Date
Feb 28, 2022
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF FLORIDA
G022 MCCARTY HALL
GAINESVILLE,FL 32611
Performing Department
Citrus Research and Education Center
Non Technical Summary
Citrus greening is considered the most serious disease in citrus worldwide, and has now reached a state of epidemic in Florida, resulting in the loss of $9 billion and over 8,000 jobs. This disease has recently been detected in California, and control strategies are crucial to prevent the collapse of the citrus industry in the US and worldwide. The disease is caused by several members of bacterial pathogens in the genus Liberibacter, that are efficiently transmitted from infected to healthy plants by psyllids, a group of plant sap-sucking insects. The control of these diseases relies on using chemical insecticides for controlling the insect vector populations, but these are still ineffective, and thus the development of sustainable control measures is urgently needed. Here I will study the factors that play a role in the bacteria movement inside the citrus plants and inside the insect vector. I will identify plant and insect genes involved in the plant-pathogen and insect-pathogen interactions, study their role in the bacterial movement, and manipulate their function for investigating their potential as targets for preventing the transmission and spread of the pathogens. The outcomes of this research will enable the development of an efficient control mechanism for this group of pathogens.
Animal Health Component
40%
Research Effort Categories
Basic
60%
Applied
40%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2120920104060%
2113110104040%
Goals / Objectives
Citrus greening has now reached a state of epidemic in Florida, resulting in the loss of $7.8 billion and over 7,000 jobs, and putting the future of Florida's citrus industry at risk. This devastating disease has now been detected in California, and control strategies are crucial to prevent the collapse of the citrus industry in the US. It is caused by the phloem-restricted bacteria Candidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. A promising approach to prevent the pathogen transmission is to interfere with the the plant-pathogen and vector-pathogen interactions, but our understanding of these processes is very limited. Moreover, we still do not understand how the bacteria move and spread inside the plant and the psyllid.In the plant CLas localize and propagate inside the phloem cells, and therefore will move between cells through the symplamic connection (i.e. sieve pores and plasmodesmata). However, there is very little knowledge about CLas movement. Association of callose with sieve areas and sieve plates in angiosperms has been widely demonstrated . It was shown that the accumulation of callose in the wall sheath around the channel results in decreased cell-to-cell movement of florescent dyes , while treatments inhibiting callose deposition resulted in an increased diameter of plasmodesmata (Pd) orifices and a higher Pd size exclusion limit (SEL) . Similar results were shown in sieve elements. Induced phloem callose led to a decrease in the lateral movement of C14-assimilates and auxin, while treatments that stimulate breakdown of sieve plate callose led to increased movement of fluorescein through the sieve tubes . Recently, a phloem-specific Callose synthase (CalS7) was identified, and its absence resulted in carbohydrate starvation . These results suggest that the presence of basal levels of callose is actually required for efficient carbohydrate transport in the phloem, and point to a more complex relationship between sieve pore callose and phloem transport, where both too much and too little callose will have a negative effect. Remarkably, it was shown that callose accumulation during CLas infection impaired symplastic dye movement into the vascular tissue, and inhibited photoassimilate export in the infected leaves , strongly suggesting that similar mechanisms take place during CLas infection.CLas is transmitted by psyllids in a persistent manner. CLas was detected in various ACP organs, including the salivary glands, hemolymph, filter chamber, midgut, fat and muscle tissues, and ovaries , suggesting that CLas propagates within the insect tissues. Previous research has suggested that CLas multiplies in nymphal stages of the ACP but not in adults , and in order to be efficiently transmitted by adults it has to be acquired in the nymphal stage and to replicate and reach sufficient amounts for transmission. Transmission rates of the CLas and CLso probably depend on the ability of the bacteria to multiply within insect tissue and reach sufficient titers for transmission, and on the ability to cross barriers during the transmission pathway especially the gut-hemolymph and the hemolyph-salivary glands barriers. The mechanism of this movement is still unknown.The goal of this work is to expand our knowledge regarding the spread of CLas inside the plant and its insect vector, and to establish novel strategies to decrease the disease symptoms of HLB infected plant by removing the callose plugs and restoring sugar transport. The specific objectives are:(a) Identify Pd associated beta-1,3-glucanases in citrus, and utilizing it to regulate callose levels.(b) Measure the sieve elements callose levels in synaptotagmins and remorins silenced plants or plants treated with auxin.(c) Study the effect of Synaptotagmins on CLas exit from ACP gut cells.
Project Methods
(a) Identification of Pd associated beta-1,3-glucanases in citrus. In Citrus sinesis, at least 33 transcripts encoding for glucan endo-1,3-β-glucosidase exist (https://phytozome.jgi.doe.gov/pz/portal.html). Using the BIG-PI Plant Predictor (http://mendel.imp.ac.at/gpi/plant_server.html), a tool that was developed to specifically identify GPI modification site prediction in plants, I have identified 12 transcripts encoding for β-1,3-glucanase proteins that are GPI anchored, two of the contain only the GH17 domain (orange1.1g043682m, orange1.1g015263m), and the other ten contain both the GH17 and X8 domains (orange1.1g010142m, orange1.1g011131m, orange1.1g011636m orange1.1g011391m, orange1.1g010782m, orange1.1g010931m, orange1.1g011532m, orange1.1g048257m , orange1.1g045344m, orange1.1g010789m). As a first step, my goal is to identify which of these 12 candidates encodes for a Pd related enzymes. Each sequence will be synthesized in such a way that the green fluorescent protein (GFP) will be located just before the GPI omega cleavage site, as described in (Levy et al., 2007; Moghadam and Jackson, 2013). These constructs will then be precipitated into the surface of the gold particles and transiently expressed in Citrus sinesis leaves by bombardment. Leaves will be analyzed by confocal scanning microscopy to identify fusion proteins that localize as puctae pattern in the cell periphery, the characteristic Pd pattern. Pd localization will be verified by staining leaf sections with aniline blue, to label Pd callose, as described in (Levy et al., 2007). Those β-1,3-glucanases that will be identified to be Pd-localized will then be cloned, without the GFP, into the PacI-StuI sited in CTV for future analysis. This is a very straightforward approach that have already been successful in tobacco (Bucher et al., 2001).(b) Measure the sieve elements callose levels in synaptotagmins and remorins silenced plants or plants treated with auxin. Citrus sinesis encodes for six synaptotagmins and eleven remorins. In collaboration with Dr. Gowda from the CREC, we have already constructed CTV-based silencing constructs for these genes. The synaptotagmin CTV clone contains nucleotides 563-941from orange1.1g009307m, which shares 90% homology to Arabidopsis SYTA. The remorin silencing CTV clone contains nucleotides 1257-1531 of orange1.1g009448m, which represents the area with the highest homology to the other members of the remoin family. These CTV clones have been already generated, semi-purified from N. benthamiana infected plants, and are now ready for citrus inoculation. Citrus macrophylla will be inoculated with these constructs, as described in (Hajeri et al., 2014). I will use quantitative RT-PCR in order to identify silenced plants. Callose levels in silenced/unsilenced leaves sieve elements will be determined by aniline blue staining, either as a result of stress (wound) or without stress. In order to avoid stress-induced callose leaves will be fixed immediately by either freezing with dry-ice or immersing in 98% ethanol. Callose levels will be determined as described in (Levy et al., 2007). In addition, I will also compare stress-induced callose by applying IAA (auxin) solution into a wound in the leaf, and compare callose levels to plants wounded without IAA.(c) Effect of Synaptotagmins on CLas exit from ACP gut cells. A bioinformatics analysis identified three clear Synaptotagmin soding sequences in the ACP genome-synaptotagmin 1-like (LOC103512870), synaptotagmin-7 (LOC103520142) and synaptotagmin-like protein 5 (LOC103516817). We will employ the CTV-based RNAi system, developed by Drs. Bill Dawson and Siddarame Gowda. I will generate CTV-RNAi constructs to silence Synaptotagmin genes in ACP. A sequence of 300 to 400 nucleotides from the corresponding gene targets RNAs. The generated CTV clone will be first agro-infiltrated into Nicotiana benthamiana plants, to establish infection. CTV virions will be isolated from systemic infected leaves of N. benthamiana, and will be used to infect Citrus macrophylla. Silencing ACP will be performed by rearing ACP nymphs on the C. macrophylla plants that were infected with the various VIGS inducing viruses, as described in (Hajeri et al., 2014). Adult psyllids will be collected and their silenced gene expression will be determined by qRT-PCR. As controls, ACPs will be reared on C. macrophylla plants infected with CTV carrying an empty vector. The accumulation of CLas in the silenced psyllids will be determined using both FISH in dissected guts, and qPCR of gut DNA. I will look for changes in bacteria accumulation levels between treated and control treated (untreated) psyllids. In addition, the longevity, fecundity, and fertility of the treated psyllids will be determined as well. Lastly, I will compare the ability of these psyllids to transmit the bacteria to healthy plants. Treated or control treated adult psyllids that carry the Liberibacter will be placed on healthy plants. After 15 days all adults and nymphs will be removed so that only eggs will be left, and new emerging adults will be collected. The transmission of the bacteria into these new adults will be determined by both quantitative PCR and FISH.Ammar, E.-D., Shatters, R.G., Jr., and Hall, D.G. (2011). Localization of Candidatus Liberibacter asiaticus, Associated with Citrus Huanglongbing Disease, in its Psyllid Vector using Fluorescence in situ Hybridization. Journal of Phytopathology 159, 726-734.Bucher, G.L., Tarina, C., Heinlein, M., Di Serio, F., Meins, F., Jr., and Iglesias, V.A. (2001). Local expression of enzymatically active class I beta-1, 3-glucanase enhances symptoms of TMV infection in tobacco. Plant J 28, 361-369.Hajeri, S., Killiny, N., El-Mohtar, C., Dawson, W.O., and Gowda, S. (2014). Citrus tristeza virus-based RNAi in citrus plants induces gene silencing in Diaphorina citri, a phloem-sap sucking insect vector of citrus greening disease (Huanglongbing). Journal of Biotechnology 176, 42-49.Levy, A., Erlanger, M., Rosenthal, M., and Epel, B.L. (2007). A plasmodesmata-associated beta-1,3-glucanase in Arabidopsis. Plant J 49, 669-682.Moghadam, P.K., and Jackson, M.B. (2013). The Functional Significance of Synaptotagmin Diversity in Neuroendocrine Secretion. Frontiers in Endocrinology 4, 124.Pelz-Stelinski, K.S., Brlansky, R.H., Ebert, T.A., and Rogers, M.E. (2010). Transmission Parameters for Candidatus Liberibacter asiaticus by Asian Citrus Psyllid (Hemiptera: Psyllidae). Journal of Economic Entomology 103, 1531-1541.

Progress 10/01/20 to 09/30/21

Outputs
Target Audience:This work was presented to the scientific communitee in the 2021 American Pytopathological Society Plant Health meeting, and the 2021 EMBO workshop onIntercellular communication and plasmodesmata in plant development and disease. Parts of the project were also presented to the citrus industry stakeholders in athe 2021 Citrus Expo meeting in Fort Mayers, FL. Changes/Problems:Due to the COVID-19 pandemictimes, we only had a limited number of people working in the lab, and this delayed our progress. Another problem was that we couldnt see a difference when we downreguated two beta-1,3-glucanases. We are going to try other callose regulators. What opportunities for training and professional development has the project provided?During this year, we had one graduate student and two post docs involved in this research, and they trained on molecular and cellular biology in my lab. A graduate student presented this work in the American Phytopathological Society southern division meeting in 2021. How have the results been disseminated to communities of interest?Results were presented to the citrus growers by a talk given in the Citrus Expo growers meeting, in Fort Mayers, FL, on August 2021. Results were published in citrus growers trade journal (Citrus Industry) on August 2021. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period we will continue to try to identify genes related to CLas movement and phloem callsoe regulation. We will use RNAi to downregulate these genes in the insect and plant. In the insect we will use dsRNA feeding, and in the plant we will employ Virus Induced Gene Silencing. We will explore the role of REMORIN proteins in HLB disease. We will study the role of beta-1,3-glucanases and Callose synthathses that we identified in our screenings incontrolling callose levels in HLB infected phloem. We will generate plants with lower expression levels of these genes with CRISPR/Cas9.

Impacts
What was accomplished under these goals? Citrus greening or Huanglongbing (HLB) disease is caused by the gram-negative bacteria Canadidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP). Currently, there are no known resistance citrus varieties, and breeding efforts were not successful so far. Spraying against the disease vector were not sufficient to block the pathogen spread as well. As an alternative, genetic engineering of resistance through biotechnology may be necessary for the long-term survival of the citrus industry. Our work goal is to identify the processes that are involved in the propagation and movement of CLas inside the plant and the insect vector. We focus in the cellular processes, and the interaction between the bacteria and the host, mainly the process of callose deposition in the plant phloem, and on membrane and vesicle trafficking in the insect gut. Better understanding of these processes could help in designing knowledge-based tools to disrupt the interaction between the ACPs and CLas and inhibiting the spread of the pathogen. Our goal is to identify a suit of candidate genes that have a confirmed function in helping or blocking CLas movement and spread. These outcomes could enable the development of an efficient control mechanism for CLas movement and transmission. During this period, we have employed the citrus seed coat vasculature to study CLas-host interactions. These organelles contain very high levels of CLas bacteria. We compared healthy and infected seed coats using microscopy and gene expression methods. We also study the difference in sugar transport and callose formation between susceptible and tolerant citrus varieties. In the insects, we analyzed the roles of endocytosis, exocytosis and autophagy related genes. (a) Identify Pd associated beta-1,3-glucanases in citrus, and utilizing it to regulate callose levels: We used the citrus tristeza virus to downregulate Callose synthase 3 in citrus, however, this method did not efficiently downregulate the gene. We used the seed coat vasculature to identify changes of genes that regulate callose levels between CLas free and CLas infected tissue. Our work identified several beta-1,3-glucanases that were differentially expressed. We also conducted RNAseq of leaves just after they were inoculated with psyllids that were either infected with CLas or not. This was done in order to identify the earliest responses to CLas inoculation. We saw that there is a strong downregulation of beta-1,3-glucanaes after inoculation with psyllids that were CLas infected, indicating that the plant accumulates callose to block the bacteria. These glucanases can be good candidates to control callose levels in the phloem. (b) Measure the sieve elements callose levels in Synaptotagmins and Remorins silenced plants or plants treated with auxin. We have been comparing callose levels in susceptible and tolerant citrus. We see lower callose levels in the tolerant varieties. Instead of auxin, we decided to use a callose inhibitor, 2-deoxy-D-glucose (2-DDG). We are spraying trees in the field and greenhouse. (c) Study the effect of Synaptotagmins on CLas exit from ACP gut cells. We identified that the autophagy process is involved in the last parts of CLas intracellular cycle in the psyllids. We have been feeding psyllids with dsRNA to inhibit their exit from the cell. We also fed psyllids with dsRNA od Synaptotagmin and evaluated the acquisition of CLas but did not see a difference.

Publications

  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Diogo Manzano Galdeano, Inaiara de Souza Pacheco, Gustavo Rodrigues Alves, La�s Moreira Granato1, Mahnaz Rashidi, Donielle Turner, Amit Levy and Marcos Antonio Machado (2020) Friend or foe? Relationship between Ca. Liberibacter spp and Diaphorina citri. Tropical Plant Pathology 45, 559571
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Yosvanis Acanda, Stacy Welker, Vladimir Orbovi?, Amit Levy. 2021. A Simple and Efficient Agroinfiltration Method for Transient Gene Expression in Citrus. Plant Cell Reports 40(7):1171-1179.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Stacy Welker, Myrtho Pierre, James P Santiago, Manjul Dutt, Christopher Vincent, Amit Levy. 2021. Phloem Transport Limitation in Huanglongbing Affected Sweet Orange Is Dependent on Phloem-Limited Bacteria and Callose. Tree Physiology DOI: https://doi.org/10.1093/treephys/tpab134
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Choaa El-Mohtar, Amit Levy. Gene therapy using citrus tristeza virus to manage HLB Disease. American Phytopathology Society southern division meeting. August 2021
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Stacy Welker, Amit Levy. Huanglongbing infection in sweet orange is associated with abnormal phloem callose deposition and carbohydrate transport disfunction. American Phytopathology Society southern division meeting. February 2021


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

Outputs
Target Audience:This work was presented to the scientific communitee in the 2020 American Pytopathological Society meeting. The project was also presented two extention presentations to the citrus growers community in two 'OJ break grower meeting' in Lake ALfred and in Siebring, Florida. Changes/Problems:The main problem this year was the COVID-19 pandemic. In some parts of theyear, labs were closed and we couldn't work, and had to throw away some materials. In other times, lab was open, but we only had a limited number of people working. This delayed our progress. An additional problem was that we were unable to perform transmission assays for CLas, and that our selected target gene did not affect CLas acquisition. We are going to test additional targets in the psyllids. What opportunities for training and professional development has the project provided?Training activities: One undergraduate and one graduate students were trained on plant molecular and cellular biology methods during this period. We also trained a visiting student from Italy in our techniqes. Professional development: Work from This work was presented in the annual American Phytopathological Society meeting, by both the PI and by the graduate student How have the results been disseminated to communities of interest?The work was presented in two extention "Orange Juice Break" activities, in Lake Alfred and in Siebring Florida. The audiance was citrus growers in Florida. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period we will continue to try to identify genes related to CLas movement. We will use RNAi to downregulate these genes in the insect and plant. We will explore the role of REMORIN proteins in HLB disease. We will identify specific beta-1,3-glucanases and Callose synthases that are controlling callose levels in HLB infected phloem. We will also conduct transcriptomic analyses to try to identify novel callose regulators in the phloem.

Impacts
What was accomplished under these goals? Citrus greening or Huanglongbing (HLB) disease is caused by the gram-negative bacteria Canadidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP). Currently, there are no known resistance citrus varieties, and breeding efforts were not successful so far. Spraying against the disease vector were not sufficient to block the pathogen spread as well. As an alternative, genetic engineering of resistance through biotechnology may be necessary for the longterm survival of the citrus industry. Our work goal is to identify the processes that are involved in the propagation and movement of CLas inside the plant and the insect vector. We focus in the cellular processes, and the interaction between the bacteria and the host, mainly the process of callose deposition in the plant phloem, and on membrane and vesicle trafficking in the insect gut. Better understanding of these processes could help in designing knowledge-based tools to disrupt the interaction between the ACPs and CLas, and inhibiting the spread of the pathogen. Our goal is to identify a suit of candidate genes that have a confirmed function in helping or blocking CLas movement and spread. These outcomes could enable the development of an efficient control mechanism for CLas movement and transmission. During the period, we continued to analyze TEM microcopy images from different tissues of the plant and insects, and identified differences between the host responses in the different tissues. We have also analized phloem transport in HLB healthy and infected plants.We have conducted different gene expression experiments to identify genes that respond to CLas in the plant and the insect. Lastly, we have used a citrus virus to downregulate a plant gene that is involved in CLas movement. (a) Identify Pd associated beta-1,3-glucanases in citrus, and utilizing it to regulate callose levels: We have combined our method to measure phloem callose with a non-invasive method to determine the phloem translocation speed in order to understand if HLB slows down phloem sugar transport in the trees. Our work determined that the presence of CLas, together with the accumulation of phloem callose, lead to phloem transport inhibition. This work showed that inhibition of callose accumulation will reverse the transport inhibition and can reduce the disease symptoms. We have analyzed the expression of different beta-1,3-glucanase genes in HLB infected and uninfected plants but saw no statistical difference in their expression. Our results determine that callose play a major role in HLB, but we still need to identify the gene players. (b)Measure the sieve elements callose levels in synaptotagmins and remorins silenced plants or plants treated with auxin: We have used a model system to study the role of Synaptotagmin and Callose Synthase 7 (CalS7). We studied the role of these two enzymes during phytoplasma infection in Arabidopsis. For Synaptotagmin, when using a mutant plant,we observed defects in the phloem sieve element structure and in the bacteria movement. In CalS7 mutants, we saw changes in the callose accumulation in the phloem and in plasmodesmata, and in the accumulation of different sugars in the phloem. We started to generate gene-edited citrus plant to reduce Synaptotagmin expression. Synaptotagmin seems to be a key target to inhibit CLas movement. (c) Study the effect of Synaptotagmins on CLas exit from ACP gut cells. We fed psyllids with dsRNA in order to reduce the expression of synaptotagmin. We confirmed the inhibition of gene expression. Next, we conducted assays to test CLas acquisition by treated insects, but did not see a major difference between treated and untreated insects. Our results suggest that int eh insect, Synaptotagmin is not a major player.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: 5. Diann Achor, Stacy Welker, Sulley K Ben-Mahmoud, Chunxia Wang , Svetlana Yuryevna Folimonova, Manjul Dutt, Siddarame Gowda, Amit Levy (2020). Dynamics of Candidatus Liberibacter Asiaticus Movement and Sieve-Pore Plugging in Citrus Sink Cells. Plant Physiology 182 (2), 882-891.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: El-Desouky Ammar, Diann Achor, Amit Levy (2019) Immuno-Ultrastructural Localization and Putative Multiplication Sites of Huanglongbing Bacterium in Asian Citrus Psyllid Diaphorina citri Insects 10 (12) DOI: 10.3390/insects10120422
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Diann Achor(&), Murad Ghanim, Stacy Welker(g), Sulley Ben-Mahmoud and Amit Levy. Lecture. Cell Biology of Candidatus Liberibacter asiaticus in Its Plant and Insect-Vector Hosts. 2020 American Phytopathology Society meeting. Aug 10, 2020
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Stacy Welker(g), Manjul Dutt, Amit Levy and Christopher Vincent. Lecture. Excessive callose formation and presence of Candidatus Liberibacter asiaticus linked to phloem transport dysfunction in citrus. 2020 American Phytopathology Society meeting. Aug 10, 2020
  • Type: Theses/Dissertations Status: Accepted Year Published: 2020 Citation: PHLOEM CALLOSE PLUGGING AND ITS ROLE IN CITRUS HUANGLONGBING DISEASE, Master thesis by Stacy Welker, 2020


Progress 10/01/18 to 09/30/19

Outputs
Target Audience:I have presented the results of our project in the "International Research Conference on Huanglongbing" meeting in Riverside, CA, I presented the result of the worktothe stakeholders influenced by the LB disease, including industry leaders and administrators. Changes/Problems:The main problem that we encountered during this period is that we could not carry out the experiments to over express plasmodesmata associated beta-1,3-glucanases. Neither transformation nor expression from viral vectors worked. It is probably very problematic to express genes that result in dramatic changes to plasmodesmata or phloem pores. We therefore decided to try three alternative methods: (1) to look for moderately expressing promoters (2) To try to downregulate callose synthase genes instead and (3) to look for additional callose regulators. In addition, with the insect, we identified ER-stress related genes that were upregulated in the infected psyllids. We will therefore study these processes in insects as well. What opportunities for training and professional development has the project provided?Training activities: One undergraduate and one graduate students were trained on plant molecular and cellular biology methods during this period. The graduate student presented a posted in the Florida Phytopathological society meeting. Professional development: Work from This work was presented in the 6th international research conference on Huanhlongbing, and the 18th international congress on molecular plant microbe interactions. How have the results been disseminated to communities of interest?Results from this work were presented at the 2019 "Citrus Show" growers meeting. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period we will continue to try to identify genes related to CLas movement. We will use RNAi to downregulate these genes in the insect and plant. We will explore the role of REMORIN proteins in HLB disease. We will identify specific beta-1,3-glucanases and Callose synthases that are controlling callose levels in HLB infected phloem. We will also conduct transcriptomic analyses to try to identify novel callose regulators in the phloem. We will study the dynamics of callose deposition in HLB infected plants.

Impacts
What was accomplished under these goals? Citrus greening or Huanglongbing (HLB) disease is caused by the gram-negative bacteria Canadidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP). Currently, there are no known resistance citrus varieties, and breeding efforts were not successful so far. Spraying against the disease vector were not sufficient to block the pathogen spread as well. As an alternative, genetic engineering of resistance through biotechnology may be necessary for the long-term survival of the citrus industry. Our work goal is to identify the processes that are involved in the propagation and movement of CLas inside the plant and the insect vector. We focus in the cellular processes, and the interaction between the bacteria and the host, mainly the process of callose deposition in the plant phloem, and on membrane and vesicle trafficking in the insect gut. Better understanding of these processes could help in designing knowledge-based tools to disrupt the interaction between the ACPs and CLas, and inhibiting the spread of the pathogen. Our goal is to identify a suit of candidate genes that have a confirmed function in helping or blocking CLas movement and spread. These outcomes could enable the development of an efficient control mechanism for CLas movement and transmission. During the period, we have developed and improved the method for transient expression in citrus using a modification to the Agro infiltration protocol. We continued to analyze TEM microcopy images from different tissues of the plant and insects, and identified differences between the host responses in the different tissues. We have conducted different gene expression experiments to identify genes that respond to CLas in the plant and the insect. Lastly, we have used a citrus virus to downregulate a plant gene that is involved in CLas movement. These finding can provide novel targets for genetic engineering that will reduce the disease symptoms associated with HLB, and inhibit or even abolish the ability of CLas to spread inside the plant and the insect vector. 1. Plasmodesmata associated beta-1,3-glucanases in citrus We have further improved the method for transient expression of genes in citrus using the gene gun. We are now using a modified Agro infiltration method that results in strong and efficient expression of desired genes in different tissues. We have tried to express plasmodesmata specific beta-1,3-glucanases in citrus, using both stable expression and citrus tristeza virus expression systems. Unfortunately we could not get good expression levels with either method. We believe that the plant cannot sustain this strong expression since it results in severe modifications to plasmodesmata and sieve pores. We are looking now for weaker promoters that will express the beta-1,3-glucanase at moderate levels. In addition we have also measured the gene-expression levels of members of the callose synthase family. We isolated the lateral vein tissue to identify phloem related genes. Gene expression analysis of lateral veins from infected grapefruit leaves, showed that CalS2, CalS5, and CalS10 were not expressed in the veins, indicating these are not responsible for phloem callose synthesis in grapefruit in response to CLas. CalS3, CalS7, CalS8, CalS9, CalS11, and CalS12 were expressed in the lateral veins. We will try to downregulate members of the CalS family as well 2. Regulation of callose levels in the citrus phloem. We have infected sweet orange plants with citrus tristeza virus (CTV) that express the sequences of citrus Synaptotagmin, in order to inhibit the gene expression using virus-induced gene silencing. These plants were then infected with CLas as well. After CLas infection we have determined that the both the Synaptotagmin gene expression levels are reduced. We developed a new methods for callose automated detection in the phloem. Using this method we were able to determine that in the Synaptotagmin downregulated plants there is less callose in the phloem. We are now comparing HLB disease symptoms in these lines and in control plants. 3. CLas exit from ACP gut cells. We used transmission electron microscopy and confocal microscopy to study the accumulation of CLas inside ACP guts. We identified novel sited where CLas seems to be replicating. These sites are probably the early form of the Liberibacter Containing Vacuoles (LCVs) we reported about earlier. We measured the gene expression of suspected players in this processes in healthy and infected psyllids. Surprisingly, in addition to genes related to vesicle trafficking, we identified different genes that are related to ER stress. We are now investigating the connection between ER stress and CLas pathogenesis.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Yosvanis Acanda, Chunxia Wang, Amit Levy (2019). Gene expression in citrus plant cells using Helios� gene gun system for particle bombardment. Methods in Molecular Biology. 2015, 219-228
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: 5. Saptarshi Ghosh , Ola Jassar, Svetlana Kontsedalov, Galina Lebedev, Chunxia Wang, Donielle Turner, Amit Levy, Murad Ghanim (2019). A Transcriptomics Approach Reveals Putative Interaction of Candidatus Liberibacter Solanacearum with the Endoplasmic Reticulum of Its Psyllid Vector. Insects 10(9), 279.


Progress 10/01/17 to 09/30/18

Outputs
Target Audience:I have presented some of our results at the Citrus Growers' Workshop on Sept. 26. The audiance in tis event was all citrus growers (25 growers). During August 2018, the part of this project that relates to bacterial movement in the insect and the plant was presented at "Citrus Expo 2018". Target audiance was the general citrus industry stakeholders, including researchers, farmers, policy makers and industry leaders Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Professional development: Prticipation and presentations in the International Conference of Plant Pathology (Boston, Massachusetts), and the 1st congress of the International Society for Citrus Huanglongbing and Liberibacter Pathosystems (Ganzhou, China) How have the results been disseminated to communities of interest?Results from this project were presented at a "Citrus growers workshop" for citrus growers, with the aim of increasing their understanding of this disease. What do you plan to do during the next reporting period to accomplish the goals?I will continue to persue the project objectives. Hopefully, during this reporting period we will gain over expression/ down regulation data for our candidate genes, and we will be able to provide some genetic data.

Impacts
What was accomplished under these goals? citrus greening or Huanglongbing (HLB) disease is caused by the gram-negative bacteria Canadidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP). Controlling this disease presents an exceptional challenge to both the industry and scientific communities. There are no known resistance citrus varieties, and therefore genetic engineered of resistance through biotechnology is one of the big hope for the long-term survival of the citrus industry. Our work goal is to identify the processes that are involved in the propagation and movement of CLas inside the plant and the insect vector, from the cellualr prespective, focusing on callose deposition in the plant phloem, and on membrane and vesicle trafficking in the insect gut. Our contribution is expected to be in designing knowledge-based tools to disrupt the interaction between the ACPs and CLas, and inhibiting the spread of the pathogen, focusing specifically on the interactions that take place inside the plant phloem and the psyllid gut. Our studies will result in a suit of candidate genes that have a confirmed function in aiding or blocking CLas movement and spread. These outcomes could enable the development of an efficient control mechanism for CLas movement and transmission that will supplement chemical sprays, and provide an urgently needed response for the US citrus industry against the greening disease. During the period of performance for this progress report of this report, we have further developed and improved ournew method for transient expression in citrus using a handheld gene-gun, to reach the phloem and other tissues.With the beta,13,glucanase we are in the process of making transgenic plants and virus constructs that express this enzyme in order to open up callose plugs. We also analized microcopy images from fifferent tissues of the plant, and identified differences between the host responses in the different tissues. Lastly, we started explporing the rople of vesicle trfficking in CLas movement inside the insect. This project is significant because these finding can provide novel targets for genetic engineering that will reduce the disease symptoms associated with HLB, and inhibit or even abolish the ability of CLas to spread inside the plant and the insect vector. 1. Plasmodesmata associated beta-1,3-glucanases in citrus We have improved our new method for transient expression of genes in citrus using the gene gun. We have optimized the system for new tissues, , and now we are able to routinely achieveexpression in the phloem tissue. We are continuing to generate new transgenic sweet orange plants, one that expresses the glucanase in all tissues, and the other expresses the enzyme only in the phloem. 2. Regulation of callose levels in the citrus phloem. We have generated citrus tristeza virus (CTV) that express the sequences of citrus Synaptotagmin and Remorin, in order to inhibit these genes expression using RNAi. We purified the virus particles from infected Nicotiana benthamiana leaves, and used them to infect Pineapple sweet orange (Citrus sinensis var. Pineapple) and C. macropylla. We were successful in obtaining CTV infected plants with the Synaptotagmin construct. In addition, we also continued to alanize transmission electron microscope images of sieve elements from various organs of CLas infected citrus. We identified a difference between the different tissues in regards to the levels of callose. Lastly, we are developing new methods for callose detection in the phloem. 3. CLas exit from ACP gut cells. We used transmission electron microscopy and confocal microscopy to study the accumulation of CLas inside ACP guts. We were able to show that vesicle trafficking is involved in CLas movement in and out of the gut cells, and that CLas co-localizes with major known regulators of exocytosis. We started to measure the gene expression of key players in this processes in healthy and infected psyllids.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Murad Ghanim, Diann Achor, Saptarshi Ghosh, Svetlana Kontsedalov, Galina Lebedev, Amit Levy (2017). ⿿Candidatus Liberibacter asiaticus⿿ Accumulate Inside Endoplasmic Reticulum Associated Vacuoles in the Gut Cells of Diaphorina citri. Scientific Reports 7, 16945.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Amit Levy, Choaa El-Mochtar, Chunxia Wang, Michael Goodin, Vladimir Orbovic (2018). A New Toolset for Protein Expression and Subcellular Localization Studies in Citrus and Its Application for Citrus Tristeza Virus Proteins Plant Methods 14 (2).


Progress 04/03/17 to 09/30/17

Outputs
Target Audience:During August 2018, the part of this project that relates to the insect transmission was presented in the "Citrus Expo 2017". Target audiance was the general citrus industrystakeholders, including researchers, farmers, policy makersand industry leaders Changes/Problems:The major change to the project is related to objective C-"Study the effect of Synaptotagmins on CLas exit from ACP gut cells". Our results from the work on this projectsuggested additional membrane rearrangement events that we were not aware of at the beginning of the project, such as the rearrangement of the endoplasmic reticulum. We intend to expand our work beyond the Synaptotagmins to other candidates that may be involved in these processes. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?I have presented a description of the project related to objective C (CLas exit from ACP gut cells) at the 2017 Citrus expo in Ft. Pierce, FL. Audience was comprised of the various members of the citrus industry, including farmers, researchers and industry leaders. What do you plan to do during the next reporting period to accomplish the goals?I intend to continue to peruse the goals that we have determined in the original application. For objective C the work will be expended beyond synaptotagmin, to other candidates that may be involved in membrane trafficking inside the psyllid.

Impacts
What was accomplished under these goals? The citrus industry is facing the tough challenge of the devastating citrus greening or Huanglongbing (HLB) disease. The disease is caused by the gram-negative bacteria Canadidatus Liberibacter asiaticus (CLas), and is transmitted by the Asian citrus psyllid (ACP). Controlling this disease presents an exceptional challenge to both the industry and scientific communities. Genetic engineered of resistance through biotechnology is the only hope for the long-term survival of the citrus industry. Our work goal is to identify the processes that are involved in the propagation and movement of CLas inside the plant and the insect vector, focusing on callose deposition in the plant phloem, and on membrane and vesicle trafficking in the insect gut. Our contribution is expected to be in designing knowledge-based tools to disrupt the interaction between the ACPs and CLas, and inhibiting the spread of the pathogen, focusing specifically on the interactions that take place inside the plant phloem and the psyllid gut. Our studies will result in a suit of candidate genes that have a confirmed function in aiding or blocking CLas movement and spread. These outcomes could enable the development of an efficient control mechanism for CLas movement and transmission that will supplement chemical sprays, and provide an urgently needed response for the US citrus industry against the greening disease. During the period of performance for this progress report of this report, we have developed a new method for transient expression in citrus using a handheld gene-gun. This method allowed us to identify a beta-1,3-glucanase (the enzymes that break down callose) from Arabidopsis that localized specifically to plasmodesmata in citrus. We are in the process of making transgenic plants that express this enzyme in order to open up callose plugs. We also identified a difference between the vegetative tissues (roots, shoots) where high levels of callose are observed and the seed coats, where very little callose is observed. Lastly, we have identified a new interaction between CLas and the psyllid endoplasmic reticulum in the insect gut cells. This project is significant because these finding can provide novel targets for genetic engineering that will reduce the disease symptoms associated with HLB, and inhibit or even abolish the ability of CLas to spread inside the plant and the insect vector. Our work can thus develop new ways to prevent CLas infection in an efficient and environmentally friendly way. Plasmodesmata associated beta-1,3-glucanases in citrus We have developed and improved our new method for transient expression of protein in citrus using the gene gun. We have optimized the system, and were able to achieve high level of expression in thousands of cells in the citrus leaves, and verified that these genes are expressing active proteins. This method worked efficiently with every citrus variety we examined (Citrus macrophylla, Carrizo, Duncan grapefruit and Madam Vinous). Using this system we expressed an Arabidopsis plasmodesmata -associated beta-1,3-glucanase in citrus, and verified it localizes to the plasmodesmata in citrus as well. We have started generating two new transgenic sweet orange plants, one that expresses the glucanase in all tissues, and the other expresses the enzyme only in the phloem. Our work enabled us to quickly identify a plasmodesmata associated beta-1,3-glucanase, and to move on to generate materials in order to test its activity. We improved the available technology for transient gene expression in citrus, and this new technology will allow citrus researchers to efficiently test gene candidates and study their activities, before moving forward to generating transgenic plants. Regulation of callose levels in the citrus phloem. We have generated citrus tristeza virus (CTV) that express the sequences of citrus Synaptotagmin and Remorin, in order to inhibit these genes expression using RNAi. We purified the virus particles from infected Nicotiana benthamiana leaves, and used them to infect Pineapple sweet orange (Citrus sinensis var. Pineapple) and C. macropylla. We were successful in obtaining CTV infected plants with the Synaptotagmin construct, but not with the Remorin. In addition, we also analyzed transmission electron microscope images of sieve elements from various organs of CLas infected citrus. We identified a difference between the vegetative tissues (roots, shoots) where high levels of callose are observed, and the seed coats, where very little callose is observed. These results can be used in order to identify new regulators of sieve pore callose in citrus phloem. CLas exit from ACP gut cells. We used transmission electron microscopy and confocal microscopy to study the accumulation of CLas inside ACP guts. We show that CLas forms a large replicative vacuole inside the ACP gut cells, and that in the presence of CLas, the psyllid endoplasmic reticulum (ER) undergoes a dramatic re-organization to associates with these intracellular bodies. Immunolocalization confirmed that CLas accumulates inside these vacuoles. Our results suggest that after entry into the gut cells, CLas modifies the host ER to create an isolated and safe environment to support its own propagation inside the psyllid. Developing treatments to prevent the formation of this CLas containing vacuole should inhibit the transmission of Clas between plants.

Publications