Herbestemmen van bestaande verbindingen als een strategie voor de identificatie van nieuwe inductoren van ziekteresistentie in planten

Pests and plant pathogens threaten global food availability. Currently, farmers heavily rely on chemical pesticides to combat these threats, but their extensive use has led to some unintended consequences, such as the emergence of resistant pathogens. Moreover, concerns have been raised about their impact on the environment and human health. Integrated pest management (IPM), a strategy that prioritizes the use of sustainable methods, is one of the tools for low-pesticide-input pest management. There is a need for new and improved plant protectants that follow the IPM strategy. Elicitors of induced resistance (IR) that activate the natural defense mechanisms of plants contribute to IPM. Since they do not exert any direct antimicrobial activity, their application is expected to have less environmental impact on beneficial organisms. Moreover, the mechanisms resulting in IR are multifaceted which is expected to reduce the chance of pathogen resistance. Still, identifying new active ingredients has become more complicated and costly. The time and development costs for new elicitors of IR can be considerably reduced by identifying new uses for existing agrochemicals. This PhD thesis aimed to identify improved plant disease treatments by repurposing existing compounds as elicitors of IR against fungi and oomycetes, using the necrotrophic fungus Botrytis cinerea and the biotrophic oomycete Hyaloperonospora arabidopsidis as model pathogens. In the first part of this PhD thesis, the reuse of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) as a novel elicitor of IR was investigated. Treatment with 2,4-D at non-herbicidal doses induced resistance in the model organism A. thaliana and the more economically relevant crop tomato. When evaluating the ability of 2,4-D to elicit IR in A. thaliana mutants of known defense pathways we could conclude that : (i) 2,4-D induced resistance (2,4-D-IR) relies on ethylene (ET) biosynthesis and signaling but does not require jasmonic acid (JA)-/ salicylic acid (SA)-mediated signaling, and (ii) camalexin biosynthesis plays a major role in 2,4-D-IR. In the second part of this PhD thesis, we screened six synthetic quaternary ammonium compounds (QUATs), originally used as antimicrobials in detergents and preservatives, as novel elicitors of IR in A. thaliana against the model pathogens. We demonstrated that the ability of the QUATs to induce resistance depends on their structure and selected benzalkonium chloride (BKC) inducing strong, IR activity at concentrations that did not exert antifungal or anti-oomycete activity in vitro. The protective effect of BKC as elicitor of IR was observed in different crops, including canola and tomato via different application methods, including leaf and root application. The induction of IR by BKC was shown to occur quickly as the protective effect of BKC-IR was already observed when the roots of tomato plants were treated up to 12 hours after B. cinerea inoculation. On the other hand, the protective effect of BKC remained until 4 days after BKC treatment. This period could be prolonged to over 5 days with an supplementary BKC treatment two days before pathogen inoculation. Aiming at a combinatorial treatment of plants with BKC and fungicides we could demonstrate that QUATs, including BKC, directly potentiated the fungicidal activity of imazalil in vitro, but unexpectedly such potentiation could not observed in planta. Interestingly, combinations of the preventive activity of BKC as an IR elicitor and the curative effect of fungicides were demonstrated to result in additive effects in planta. Indeed such combinations of BKC with the fungicide imazalil (at sub-fungicidal dose) allowed to reduce the dose of imazalil at least twofold, for a similar protective effect as a single imazalil treatment in A. thaliana, canola, and tomato against B. cinerea. Moreover, similar results were observed when combining BKC with other types of commercially available fungicides such as Scala® and Teldor®. In the final part of this PhD thesis, the molecular mechanisms underlying BKC-IR were investigated by performing a comparative transcriptomic analysis and by phenotypic evaluations. Both approaches revealed that (i) BKC-induced resistance (BKC-IR) relies on JA/SA biosynthesis and signaling and ET biosynthesis, (ii) genes encoding "Late Embryogenesis Abundant" (LEA) proteins are amongst the most upregulated differently expressed genes upon BKC treatment, (iii) the importance of one of them (AT1G52690) in BKC-IR was confirmed, and (iv) BKC significantly increases the amount of the main cell wall components hemicellulose, pectin, and cellulose in A. thaliana, thereby suggesting that BKC-IR relies (partially) on the fortification of the plant cell wall.