The in vitro CLas-hairy roots assay was performed according to the previously described protocol 28 . CLas-citrus hairy roots were generated using CLas-infected citrus plant tissues, and the diagnosis of CLas was confirmed by quantitative PCR (qPCR). CLas-hairy roots were surface sterilized, and ~100 mg was transferred into multi-well plates containing Gamborg's B-5 medium with 1% sucrose. Different concentrations of bioflavonoids (Horbaach, https://horbaach.com/products/citrus-bioflavonoids-complex-1500mg-300-vegetarian-caplets) and ferulic acid (Fisher Scientific, Catalog No. ICN10168505): 125, 250, 500, and 1000 ppm/mL, were added, vacuum infiltrated and incubated on a rotator shaker at 50 rpm in the dark at 25°C for 72 h. The experiments were carried out with six biological replicates, positive control (oxytetracycline hydrochloride), untreated CLas hairy roots, and an equal concentration of ethanol solvent used to dissolve the bioflavonoids and ferulic acid as negative controls. After the treatments, tissue samples were treated with PMAxx dye (propidium monoazide, Biotium, Fremont, CA) to inactivate dead CLas bacterial DNA. Further, total DNA was extracted, and viable bacterial titer was estimated by qPCR analysis using primers specific to the CLas gene encoding the Ribonucleotide reductase β-subunit (nrdB, RNR-F/RNR-R) 62 and the relative CLas titers were estimated and plotted relative to untreated using the 2-ΔΔCt method. After normalization of target Ct with an endogenous reference gene (Ct') glyceraldehyde3phosphate dehydrogenase 2 (GAPC2) 63 to correct for DNA template concentration differences among the samples, it was plotted relative to untreated controls. -severe HLB symptoms). b) A close-up of a network cluster showing distributions of molecular abundances in trees with different disease ratings (higher values correspond to higher symptom severity); node size is related to total compound abundance. The compounds in the cluster were present in higher amounts when the disease was more severe. The selected example shows perturbation in amounts of tryptophan, indicative of altered metabolism, and a metabolite known to be of microbial origin, indole-3-lactic acid (ILA), a tryptophan metabolite that is known to play a role in microbe-host interactions; ILA is associated with increased disease severity. c) A supervised analysis (partial least squares discriminant analysis, PLSDA) of tissues from trees in orchards across Florida showed metabolome stratification according to disease severity. The analysis indicates differences in metabolomes associated with disease severity (Q2 0.1775). d) Unsupervised analysis (principal component analysis, PCA) of tissues from greenhouse-reared trees indicated drastic differences in the metabolome of healthy and infected symptomatic tissues.