Epigenetic weapons in plant-herbivore interactions: Sulforaphane disrupts histone deacetylases, gene expression, and larval development in Spodoptera exigua while the specialist feeder Trichoplusia ni is largely resistant to these effects

Cruciferous plants produce sulforaphane (SFN), an inhibitor of nuclear histone deacetylases (HDACs). In humans and other mammals, the consumption of SFN alters enzyme activities, DNA-histone binding, and gene expression within minutes. However, the ability of SFN to act as an HDAC inhibitor in nature, disrupting the epigenetic machinery of insects feeding on these plants, has not been explored. Here, we demonstrate that SFN consumed in the diet inhibits the activity of HDAC enzymes and slows the development of the generalist grazer Spodoptera exigua, in a dose-dependent fashion. After consuming SFN for seven days, the activities of HDAC enzymes in S. exigua were reduced by 50%. Similarly, larval mass was reduced by 50% and pupation was delayed by 2-5 days, with no additional mortality. Similar results were obtained when SFN was applied topically to eggs. RNA-seq analyses confirm that SFN altered the expression of thousands of genes in S. exigua. Genes associated with energy conversion pathways were significantly downregulated while those encoding for ribosomal proteins were dramatically upregulated in response to the consumption of SFN. In contrast, the co-evolved specialist feeder Trichoplusia ni was not negatively impacted by SFN, whether it was consumed in their diet at natural concentrations or applied topically to eggs. The activities of HDAC enzymes were not inhibited and development was not disrupted. In fact, SFN exposure sometimes accelerated T. ni development. RNA-seq analyses revealed that the consumption of SFN alters gene expression in T. ni in similar ways, but to a lesser degree, compared to S. exigua. This apparent resistance of T. ni can be overwhelmed by unnaturally high levels of SFN or by exposure to more powerful pharmaceutical HDAC inhibitors. These results demonstrate that dietary SFN interferes with the epigenetic machinery of insects, supporting the hypothesis that plant-derived HDAC inhibitors serve as epigenetic weapons against herbivores.

Automated summary

Cruciferous plants produce sulforaphane (SFN) which acts as an inhibitor of histone deacetylases (HDACs). Consuming SFN can alter enzyme activities, DNA-histone binding, and gene expression in mammals within minutes. This study demonstrates that SFN can also inhibit HDAC enzymes in insects, leading to slower development in a dose-dependent manner. However, specialist feeder insects like Trichoplusia ni are not negatively affected by SFN, suggesting a potential co-evolutionary adaptation. These findings suggest that plant-derived HDAC inhibitors serve as epigenetic weapons against herbivores.