Metabolic modeling of a plant-pathogen interaction quantifies the metabolic bottlenecks underlying bacterial wilt

During plant infection, complex metabolic interactions occurs between host and pathogen, including a genuine competition for resources. While the pathogen exploits host nutrients to support its growth and virulence, the plant attempts to restrict pathogen multiplication by limiting nutrient availability or producing antimicrobial compounds. To unravel these trophic interactions, we constructed a genome-scale metabolic model of a complete pathosystem by integrating a multi-organ metabolic model of the plant, a pathogen metabolic model, quantitative measurements, and a mathematical framework based on sequential flux balance analyses (FBAs). This strategy was applied to the Ralstonia pseudosolanacearum-tomato system. For the first time, quantitative fluxes of matter occurring during a plant infection were predicted. The model shows that (i) plant photosynthetic capacity is a stronger constraint than mineral availability for bacterial proliferation, (ii) infection-induced reduction of plant transpiration limits and ultimately halts first plant growth, then pathogen expansion, (iii) stem resource hijacking can enhance bacterial growth but remains secondary, and (iv) pathogen-excreted putrescine is likely reused for the plants needs. This study delivers the first holistic and quantitative representation of trophic interactions within a plant-pathogen system and highlights the central importance of water flow when the infectious agent is a fast-growing, xylem-colonizing bacterium.