The blast pathogen effector AVR-Pik binds and stabilizes rice heavy metal-associated (HMA) proteins to co-opt their function in immunity

PLoS Pathog. 2024 Nov 18;20(11):e1012647. doi: 10.1371/journal.ppat.1012647. eCollection 2024 Nov.

Abstract

Intracellular nucleotide-binding domain and leucine-rich repeat-containing (NLR) receptors play crucial roles in immunity across multiple domains of life. In plants, a subset of NLRs contain noncanonical integrated domains that are thought to have evolved from host targets of pathogen effectors to serve as pathogen baits. However, the functions of host proteins with similarity to NLR integrated domains and the extent to which they are targeted by pathogen effectors remain largely unknown. Here, we show that the blast fungus effector AVR-Pik binds a subset of related rice proteins containing a heavy metal-associated (HMA) domain, one of the domains that has repeatedly integrated into plant NLR immune receptors. We find that AVR-Pik binding stabilizes the rice small HMA (sHMA) proteins OsHIPP19 and OsHIPP20. Knockout of OsHIPP20 causes enhanced disease resistance towards the blast pathogen, indicating that OsHIPP20 is a susceptibility gene (S-gene). We propose that AVR-Pik has evolved to bind HMA domain proteins and co-opt their function to suppress immunity. Yet this binding carries a trade-off, it triggers immunity in plants carrying NLR receptors with integrated HMA domains.

MeSH terms

  • Ascomycota / metabolism
  • Disease Resistance
  • Fungal Proteins / metabolism
  • Host-Pathogen Interactions / immunology
  • Metals, Heavy / metabolism
  • NLR Proteins / metabolism
  • Oryza* / immunology
  • Oryza* / metabolism
  • Oryza* / microbiology
  • Plant Diseases* / immunology
  • Plant Diseases* / microbiology
  • Plant Immunity*
  • Plant Proteins* / metabolism

Substances

  • Plant Proteins
  • Fungal Proteins
  • Metals, Heavy
  • NLR Proteins

Grants and funding

This work was supported by the Japan Society for Promotion of Science Grant, grants numbers 15H05779, 20H05681, 23K20042, and 24H00010 to RT, grant 21K14834 to MS, grant 18K05657 to HS. This work was further supported by JSPS/The Royal Society Bilateral Research for the project “Retooling rice immunity for resistance against rice blast disease” (2018-2019) to SK and MJB, UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Norwich Research Park Biosciences Doctoral Training Partnership, UK, BB/M011216/1 to MJB, UKRI BBSRC, UK, BB/W00108X/1, BB/P012574, BB/M02198X, SK and MJB, European Research Council, ERC proposal 743165, SK and MJB, the Gatsby Charitable Trust to SK, the John Innes Foundation to MJB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.