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Purinergic signaling activated by extracellular nucleotides and their derivative nucleosides trigger sophisticated signaling networks. The outcome of these pathways determine the capacity of the organism to survive under challenging conditions. Both extracellular ATP (eATP) and Adenosine (eAdo) act as secondary messengers in mammals, essential for immunosuppressive responses. Despite the clear role of eATP as a plant damage-associated molecular pattern, the function of its nucleoside, eAdo, and of the eAdo/eATP balance in plant stress response remain to be fully elucidated. This is particularly relevant in the context of plant/microbe interaction, where the intruder manipulates the extracellular matrix. Here, we identify Ado as a main elicitor secreted by the vascular fungus Fusarium oxysporum. We show that eAdo modulates the plant’s susceptibility to fungal colonization by altering eATP-mediated physiological immune responses, such as apoplastic pH and calcium homeostasis. Our work indicates that plant pathogens actively imbalance the eAdo/eATP levels as a virulence mechanism.

The apoplastic Adenosine/ATP balance is a messenger for plant defense and can be manipulated by the fungal pathogen F. oxysporum.