Rapid breakdown of Cf-6 -mediated immunity in tomato through loss or mutation of the Avr6 effector gene in Fulvia fulva

作者：Christiaan R. Schol, Like Fokkens, A-Li Hu, Ruifang Jia, Silvia de la Rosa, Bilal Ökmen, Anne M. Hilgers, Samuel L. van Zwoll, Luuk D. H. Veenendaal, Marie Turner, C. Monot, Kazuya Maeda, Yuichiro Iida, Alex Z. Zaccaron, Ioannis Stergiopoulos, Pierre J.G.M de Wit, Danny Esselink, Anne-Marie A. Wolters, Yuling Bai, M.H.A.J. Joosten, Carl H. Mesarich · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.06.11.659170 · 研究领域：Plant-Microbe Interactions and Immunity、Plant Disease Resistance and Genetics、Plant Pathogens and Fungal Diseases

Summary Genetic resistance mediated by Cf cell-surface receptors is a cornerstone of tomato breeding against leaf mold disease caused by the fungal pathogen Fulvia fulva . After widespread deployment of the Cf-9 resistance locus, breeders increasingly relied on Cf-6 , yet Cf-6 -mediated resistance has already been overcome in multiple regions. The molecular basis of this breakdown, and the identity of the matching avirulence (Avr) effector, have remained unresolved. Here, we use comparative genomics and functional genetics to identify the F. fulva effector Avr6 as the previously described apoplastic protein Ecp5. Sequencing of Cf-6 -breaking strains revealed either deletion of the Ecp5 locus or non-synonymous mutations in its coding sequence. Using transient expression, targeted gene knockout, and complementation assays, we show that Ecp5 is both necessary and sufficient for Cf-6-mediated recognition and defence activation. We then use Avr6-triggered cell death as a phenotypic marker in a bulked segregant analysis combined with Comparative Subsequence Sets analysis (CoSSa) to map Cf-6 to a ∼2 Mb interval on the short arm of chromosome 12 that overlaps the previously described Cf-Ecp5.12 locus. Sequencing of Avr6 in a broad strain collection reveals a predominantly conserved allele under apparent purifying selection, with recent independent loss-of-function variants in Europe and South America that confer virulence on Cf-6 plants. Together, these findings establish the Avr6–Cf...