Non-steroidal anti-inflammatory drugs help to enhance crop genome editing tools, study says

According to plant scientists at RIKEN, a class of non-steroidal anti-inflammatory drugs (NSAIDs) might be useful for studying the molecular processes underlying plant immunity. Their findings might potentially aid in the development of crop genome-editing tools.

Non-steroidal anti-inflammatory drugs help to enhance crop genome editing tools, study says
An Arabidopsis plant model provided RIKEN researchers with a way of testing hundreds of chemicals to determine how they interacted with plant immune responses. They found that, while most non-steroidal anti-inflammatory drugs (NSAIDs) boost plant immunity, three oxicam-type NSAIDs suppressed it. Image Credit: 2022 RIKEN Center for Sustainable Resource Science

Many NSAIDs, like aspirin, are generated from salicylic acid, a plant defense signaling hormone. Salicylic acid levels rise in plants respond to the pathogenic virus, fungus, and bacterial infections. Plants’ immunological responses can be boosted by using salicylic acid as an external therapy. However, the exact processes governing salicylic-acid signaling pathways remain unknown, partially due to the compound’s various functions and diverse actions in different plants.

Ken Shirasu of the RIKEN Center for Sustainable Resource Science has studied plant immunology for many years. Ken discovered that salicylic acid triggers immunological signaling in 1997. Plants use salicylic acid activity to promote local cell death as a critical defense response when they come into contact with a pathogen.

Chemical genetics has come a long way since then, and so I decided to return to my initial experiment with my team here at RIKEN. We re-established the assay using a cell-culture system of the model plant Arabidopsis.”

Ken Shirasu, Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science

Shirasu’s team utilized the gene encodes NPR1, a major regulator of immunity-related genes, as a measure of salicylic-acid activity in their model because they knew salicylic acid reacts with an NPR1 protein. When plants were treated with the bacteria that cause bacterial speck disease, the researchers looked at whether additional NSAIDs may help enhance plant defense.

Researchers were able to quickly screen hundreds of compounds using the cell-culture technique to uncover salicylic-acid functional analogs that produced immune-mediated cell death.

Most of the chemicals we tested initiated immune responses similar to those of salicylic acid, but we found three ‘oxicam-type’ NSAIDs that instead suppressed immunity signaling. This was very curious.”

Ken Shirasu, Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science

When the researchers looked at the function of tenoxicam, the most powerful of the three, they discovered that it blocks the NPR1 protein from aggregating in cell nuclei.

We believe tenoxicam upregulates oxidative stress-related genes, inducing oxidation and altering cellular redox status. NPR1 is regulated by redox status, so this disruption inhibits the plant’s salicylic-acid pathway. These NSAIDs provide a unique tool to dissect the salicylic-acid signaling pathway and improve our understanding of plant immunity.”

Ken Shirasu, Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science

This discovery might have applications in genome editing. Although Agrobacterium is frequently employed to genetically modify plants, certain crops are resistant to infection. Oxicam-type NSAIDs may be able to turn off immunity, allowing transformation to take place.

Source:
Journal reference:

Ishihama, N., et al. (2021) Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway. Nature Communications. doi.org/10.1038/s41467-021-27489-w.

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