The “grove-first” framework: Starting in the grove to find therapies for huanglongbing

Authors: Heck, Michelle; Larson, Nicholas; LOCATELLI, GUILHERME - University Of Florida; COCHRANE, ELLEN - University Of Florida; CORADETTI, SAMUEL - Cornell University; HALLMAN, LUKAS - University Of Florida; JOHNSON, LYNN - Cornell University; ESTES, W. CODY - Estes Citrus Inc; Makar, Ariana; DEMIRDEN, NURSENA - Oak Ridge Institute For Science And Education (ORISE); Pitino, Marco; Shatters, Robert; ADAIR, ROBERT - Florida Research Center For Agricultural Sustainability (FLARES); GILES, FRANK - Consultant; FOX, JOHN PAUL - University Of Florida; STEUHLER, DOUGLAS - Oak Ridge Institute For Science And Education (ORISE); HODGE, JOANNE - University Of Florida; HOFFMAN, JAMES - Estes Citrus Inc; BLAKE, VICTORIA - Indian River State College; ULYSSE, LOUSHENDY - Indian River State College; RAMIREZ-BARREA, LISVET - Indian River State College; ZAMBONE, FLAVIA - University Of Florida; SHENDE, KETAN - University Of Florida; ROSSI, LORENZO - University Of Florida; MCKENNA, RILEY - Consultant; D'ELIA, TOM - Indian River State College; SCULLY, BRIAN - Retired ARS Employee; Niedz, Randall

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 5/18/2025
Publication Date: 5/23/2025
Citation: Heck, M.L., Larson, N.R., Locatelli, G., Cochrane, E., Coradetti, S., Hallman, L., Johnson, L., Estes, W., Makar, A.K., Demirden, N., Pitino, M., Shatters, R.G., Adair, R., Giles, F., Fox, J., Steuhler, D., Hodge, J., Hoffman, J., Blake, V., Ulysse, L., Ramirez-Barrea, L., Zambone, F., Shende, K., Rossi, L., Mckenna, R., D'Elia, T., Scully, B., Niedz, R.P. 2025. The “grove-first” framework: Starting in the grove to find therapies for huanglongbing. bioRxiv. https://doi.org/10.1101/2025.05.22.655577.
DOI: https://doi.org/10.1101/2025.05.22.655577

Interpretive Summary: Huanglongbing (HLB), or citrus greening, continues to devastate groves around the world, and conventional lab-to-field testing pipelines are too slow to keep pace with the urgent needs of citrus growers. The Grove-First framework turns this process on its head by starting where it matters most, in productive, HLB-infected trees in the grove, so that only treatments that show real-world benefit move forward. By coupling direct trunk-injection technology with a drug-repurposing strategy, the team rapidly screened regulatory-friendly compounds in 8-year-old Valencia orange trees over a single growing season. Several candidates equaled or out-performed the current industry standard, oxytetracycline, in both tree-health ratings and fruit-yield metrics. Because many of these chemistries already have well-characterized safety profiles, some can be deployed immediately, while others are fast-tracked for further regulatory review. Overall, Grove-First compresses a multi-year discovery pipeline into months, bringing practical, science-backed solutions and renewed profitability within reach of citrus growers far sooner than traditional approaches.

Technical Abstract: Citrus greening disease, also known as huanglongbing (HLB), is one of the most serious bacterial diseases of citrus world-wide. There is an immediate global need to provide the citrus industry with relief from HLB and a return to profitable citrus production. Standard screening methods for HLB therapeutic treatments typically involve various laboratory-based assays to select treatments with antimicrobial properties1, which then advance to greenhouse and eventually field testing in a scheme that takes multiple years. In the United States, despite spending over $1.4 billion dollars on HLB research and generating new knowledge on the disease and vector, no solutions to manage the disease in a productive grove have advanced from the research community to the commercial grower2. Here, we present a design of experiments framework3, referred to as Grove-First, to rapidly screen treatments in bearing citrus trees using direct trunk injection to select treatments that improve tree health and fruit yield over the course of a single growing season. A drug repurposing approach enabled us to screen chemistries with regulatory-friendly profiles for rapid industry adoption. Using this framework, we identified candidate treatment chemistries with effects comparable to or better than oxytetracycline (OTC) on visual tree-health and yield indices in an initial screen of HLB-positive 8-year-old Valencia trees. These candidates are now under investigation for consistency and robustness of those effects. Grove-First rapidly accelerated the identification and large-scale field testing of HLB therapies, some of which are available for growers to use immediately and others that require further regulatory actions.