A fungal endophyte-generated nucleoside signal regulates host cell death and promotes root colonization

Efficient intracellular colonization of roots by the beneficial fungal endophyte Serendipita indica requires restricted host cell death. How this symbiotic host cell death is initiated and controlled is largely unknown. Here we show that two fungal enzymes, the ecto-5-nucleotidase SiE5NT and the nuclease SiNucA, act synergistically in the apoplast at the onset of cell death to produce deoxyadenosine (dAdo), a potent cell death inducer in animal systems. Uptake of extracellular dAdo, but not of the structurally related adenosine (Ado), activates a previously undescribed cell death mechanism in plants. Mutation of the A. thaliana equilibrative nucleoside transporter ENT3 confers resistance to extracellular dAdo-triggered cell death and leads to decreased fungal-mediated cell death during root colonization. A library screen of A. thaliana T-DNA insertion lines identified an NLR as an additional intracellular component in dAdo-triggered cell death, establishing a link to immunometabolism in plants. ### Competing Interest Statement The authors have declared no competing interest.