Integrated Analysis of Citrus Molecular Responses to CLas: Towards Mechanistic Understanding

Huanglongbing (HLB), primarily caused by ‘Candidatus Liberibacter asiaticus’ (CLas), threatens global citrus production. Deciphering the molecular interplay between citrus and CLas is crucial for successful control. This review synthesizes current understanding of the molecular mechanisms underlying citrus-CLas interactions, providing a comprehensive overview that spans immune signaling, hormonal and metabolic reprogramming, non-coding RNA-mediated regulation, pathogen effector biology, and emerging biotechnological interventions. We detail the hierarchical host response: initial immune recognition via pattern recognition receptors, triggering reactive oxygen species bursts and calcium signaling. Moreover, hormonal network reprogramming and their complex interplay in defense/susceptibility are examined. Transcriptomic studies have revealed key features of metabolic reprogramming, including suppression of photosynthesis and impairment of phloem function. Additionally, long-term strategies like cell wall reinforcement, accumulation of defensive compounds such as flavonoids and terpenoids, and roles of post-transcriptional regulation of microRNAs are discussed. Conversely, CLas counter-defense, notably effector-mediated immunity suppression and host metabolism manipulation, is also considered. Comparative transcriptomics between tolerant and susceptible varieties identifies tolerance or resistance genes/pathways for breeding and engineering. Despite this progress, critical knowledge gaps remain, particularly regarding the precise molecular mechanisms of CLas immune evasion and effector-mediated suppression, the genetic basis of natural tolerance, and the field-level efficacy of defense priming strategies. Future research directions should integrate single-cell omics, CRISPR/Cas9 editing, nano-enabled delivery, and microbiome engineering to bridge these gaps and accelerate HLB-tolerant/resistant citrus development. This review synthesizes how molecular profiling advances understanding of citrus defense mechanisms against HLB, and underscores the imperative for interdisciplinary research and global collaboration.