Breeding for Durable Resistance in the Era of Gene Editing: From R-Genes to Susceptibility (S)-Gene Knockouts

Abstract

The quest for durable disease resistance in crops has entered a transformative era with the convergence of genomic discovery and precision gene editing technologies. Traditional breeding has been successful in providing resistance (R) genes, but they typically provide only race-specific resistance that can be easily overcome by evolution of the pathogens. Susceptibility (S) genes, however, are plant genes that pathogens use to infect plants, and are a completely different target for resistance breeding. Loss-of-function mutations in S genes may provide broad-spectrum and possibly more persistent resistance, since pathogens may not be able to overcome host factors that they require for their growth. This review summarizes what is known about R-gene and S-gene mediated resistance, and discusses the mechanisms underlying the function of the S-gene for various groups of pathogens. Targeted S-gene knockout using CRISPR/Cas technology, including successful case studies in powdery mildew resistance (via MLO), virus resistance (via eIF4E) and bacterial blight resistance (via SWEET promoter), is evaluated. The challenge of growth-defense trade-offs that arise when disrupting the S-gene is critically discussed, and novel methods to reduce such costs, such as precise regulatory editing, tissue-specific expression and identification of natural alleles of loss of function, are explored. S-gene targeting, along with the recently developed multiplex genome editing techniques, combined with the emerging multi-omics data for the discovery of S-genes, makes this a key method for the next generation of crop improvement. Finally, future directions are presented, such as the potential for multi-gene pyramiding of R genes, in combination with S gene editing, to provide high and durable disease resistance in the context of climate change and changing the population of pathogens.