Bois noir is a disease associated with the presence of phytoplasma 'Candidatus Phytoplasma solani' belonging to the Stolbur group (subgroup 16SrXII-A), which has a heavy economic impact on grapevines. This study focused on the changes induced by phytoplasma in terms of the profile and amount of secondary metabolites synthesized in the phenylpropanoid pathway in leaves of Vitis vinifera L. red-berried cultivar Sangiovese. Metabolic alterations were assessed according to the disease progression through measurements of soluble sugars, chlorophyll, and phenolic compounds produced by plant hosts, in response to disease on symptomatic and asymptomatic Bois noir-positive plants. Significant differences were revealed in the amount of soluble sugars, chlorophyll, and accumulation/reduction of some compounds synthesized in the phenylpropanoid pathway of Bois noir-positive and negative grapevine leaves. Our results showed a marked increase in phenolic and flavonoid production and a parallel decrease in lignin content in Bois noir-positive compared to negative leaves. Interestingly, some parameters (chlorophyll a, soluble sugars, total phenolic or flavonoids content, proanthocyanidins, quercetin) differed between Bois noir-positive and negative leaves regardless of symptoms, indicating measurable biochemical changes in asymptomatic leaves. Our grapevine cultivar Sangiovese results highlighted an extensive modulation of the phenylpropanoid biosynthetic pathway as a defense mechanism activated by the host plant in response to Bois noir disease.Pathogens 2020, 9, 269 2 of 17 This strain is transmitted from plant-to-plant above all by Hyalesthes obsoletus Signoret (Homoptera: Cixiidae), a polyphagous leafhopper, which has various hosts that act as phytoplasma reservoirs [5].The symptoms on infected plants depend on the variety, but generally, different visual symptoms are exhibited, such as stunting, abnormal lignification of canes, short internodes, flower abortion, downward curling, and yellowing and/or reddening leaves, resulting in severe yield reduction and even plant death [6].A number of mechanisms by which phytoplasmas induce disease symptoms have been proposed: through the production of phytoplasma-secreted proteins (effectors), which play an important role in host-pathogen interactions and pathogenicity eliciting the disease symptoms [7]. The latter include yellowing or reddening leaves, in relation to white-or red-berried grape varieties respectively, induced by phytoplasma are associated with an alteration in the use of sugars in the phloem [8,9]. In fact, several studies have reported evidence of extensive modification in the synthesis and transport of soluble carbohydrates and starch, a decrease in photosynthetic activity, the breakdown of chlorophyll, carotenoids, and their biosynthesis inhibition in many phytoplasma-infected plants, including in Vitis spp. [8,[10][11][12][13]. In BN-infected grapevine of white-berried cv. Chardonnay, symptoms have been related to reduced photosynthetic activity and the anomalous ...