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One century after the first report of Dutch elm disease (DED), there is still no practical solution for this problem threatening European and American elms ( Ulmus  spp.). The long breeding cycles needed to select resistant genotypes and the lack of efficient treatments keep disease incidence at high levels. In this work, the expression of defense-related genes to the causal agent of DED,  Ophiostoma novo-ulmi  Brasier, was analyzed in in vitro clonal plantlets from two DED-resistant and two DED-susceptible  Ulmus minor  Mill. trees. In addition, the effect of the inoculation of an endophytic pink-pigmented yeast ( Cystobasidium  sp.) on the plant’s defense system was tested both individually and in combination with  O. novo-ulmi . The multifactorial nature of the resistance to DED was confirmed, as no common molecular response was found in the two resistant genotypes. However, the in vitro experimental system allowed discrimination of the susceptible from the resistant genotypes, showing higher levels of oxidative damage and phenolic compounds in the susceptible genotypes after pathogen inoculation. Inoculation of the endophyte before  O. novo-ulmi  attenuated the plant molecular response induced by the pathogen and moderated oxidative stress levels. Niche competition, endophyte–pathogen antagonism and molecular crosstalk between the host and the endophyte are discussed as possible mechanisms of stress reduction. In sum, our results confirm the complex and heterogeneous nature of DED resistance mechanisms and highlight the possibility of using certain endophytic yeasts as biological tools to improve tree resilience against biotic stress.

No priming, just fighting—endophytic yeast attenuates the defense response and the stress induced by Dutch elm disease in Ulmus minor Mill.