A research team led by Jian Ye from the Institute of Microbiology of the Chinese Academy of Sciences has identified the first mechanism of citrus resistance to HLB. Results of the study were published in Science.
Utilizing artificial intelligence (AI), the team has also developed antimicrobial peptides that offer a promising therapeutic approach to combat the disease. This discovery addresses the absence of naturally occurring HLB-resistant genes in citrus.
HLB has devastated millions of acres of citrus crops across 50 countries in Asia, Africa, the Americas and Europe. All commercial citrus varieties are susceptible. Once infected, trees typically perish within a few years.

To address this issue, the researchers identified a key resistance pathway involving the transcription factor MYC2 and its interacting E3 ligase, PUB21. By examining citrus species and their distant relatives in the Rutaceae family, they discovered PUB21 paralogs in Bergera koenigii (curry leaf plant) and Zanthoxylum bungeanum (Sichuan pepper plant). These paralogs encode a dominant-negative form of PUB21 (PUB21DN), featuring a crucial mutation at residue 39 that suppresses PUB21 activity. This suppression stabilizes the MYC2 protein and significantly enhances defense pathways and antibacterial metabolites production, conferring immunity to HLB. Transgenic citrus plants engineered to overexpress PUB21DN demonstrated increased resistance to the disease.
Building on these natural resistance mechanisms, the researchers used AI-driven screening technology to stabilize MYC2 by inhibiting PUB21 activity. Through this approach, they identified a group of anti-proteolysis peptides (APPs), including APP3-14, which showed promising results in both greenhouse and field trials. APP3-14 not only effectively controlled the HLB-causing pathogen CLas but also disrupted disease transmission, achieving up to 80% control efficiency in a single season.
This finding offers a dual benefit: the development of druggable peptides for eco-friendly biopesticides and a novel strategy to combat uncultivable pathogens through targeted protein stabilization. Beyond HLB, this strategy could help address other plant diseases caused by difficult-to-culture pathogens.
Source: Chinese Academy of Sciences
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