Researchers Find Plant Immune System's 'Take Two Aspirin' Gene, Offering Hope For Disease Control Without Agricultural Pesticides

Discovery of the salicylic acid-binding protein 2 (SABP2) gene, by scientists at Boyce Thompson Institute for Plant Research (BTI) at Cornell University, is being called an important step toward new strategies to boost plants' natural defenses against disease and for reducing the need for agricultural pesticides.

Salicylic acid, the chemical compound found naturally in most plants (as well as in the most-used medication, aspirin), is a plant hormone produced at elevated levels in response to attack by microbial pathogens. According to a report on the Web today in the Proceedings of the National Academy of Sciences (PNAS Early Edition, week of Dec. 7, 2003) by BTI's Dhirendra Kumar and Daniel F. Klessig, the aspirin-like hormone is perceived by the SABP2 protein and a message is transmitted, via a lipid-based signal, to activate the plant's defense arsenal. Says Klessig, "Now that we know a key signaling protein in plant immune systems, we can work on ways to enhance the signal and help plants fight disease without using potentially harmful pesticides."

The PNAS authors say SABP2 plays an important role in restricting infections by inducing host cells at the site of infection to undergo programmed cell death and sacrifice themselves for the benefit of the rest of the plant.

SABP2 also plays a critical role in activating the innate immune system in other parts of the plant to guard against further attack or spread by the same pathogen – and even against unrelated pathogens. (Innate immune systems, which mount an immediate defense against infections, are found in all plants and animals. But only vertebrates, including humans and other mammals, have additional levels of defense – the antibody-producing B cell and T cell-mediated acquired immunity for a delayed response that can take weeks to develop.)

The Klessig laboratory discovered the presence of the SABP2 protein in plants in 1997. But it took five years to purify the protein, which occurs naturally in "excruciatingly small amounts," then to clone the gene that encodes it, and finally to assess the role of SABP2 in disease resistance. The PNAS article tells how the researchers proved that SABP2 is a key player in innate immunity by silencing the SABP2 gene and watching the plant immune system fail.

Although the salicylic acid-signaling experiments were done with tobacco plants – because tobacco is a well-known plant species for studying disease resistance – similar salicylic acid-binding proteins are found in other plant species, the BTI researchers say, making their results applicable to other crop plants.

And the finding might even help immunologists understand evolutionarily related signaling pathways in vertebrates, including humans, according to another BTI researcher and professor of plant pathology at Cornell, Gregory B. Martin. In a 2001 research article, he suggested that some molecular mechanisms involved in innate immunity in mammalian and insect systems "are remarkably similar to the molecular mechanisms underlying plant disease-resistance responses." Innate immunity in all kinds of living things, Martin and his co-authors added, "might be an evolutionarily ancient system of host defense."

When tobacco mosaic virus attacks a tobacco plant, the PNAS authors report, the immediate visible effect of SABP2 is to enable salicylic acid to induce the so-called hypersensitive resistance response. "We see programmed cell death at the site of the attack as plant cells sacrifice themselves for the overall survival of the plant," Klessig explains. "We believe programmed cell death helps restrict the infection to a small part of the plant. Something similar happens in animal systems, when virus-infected cells or cells with defective growth control that could become cancerous undergo programmed cell death," he says, noting that aspirin has been found to have a protective effect against cancer.

Even as the infection is being contained, the plant begins to signal other parts of itself that it is undergoing attack. "This leads to long-lasting, broad-spectrum systemic resistance to infections against the initial attacking pathogen and also against other viral, bacterial and fungal pathogens," Klessig says. "Systemic acquired resistance can last throughout most of the life of an annual plant."

Earlier this year the Klessig research group announced (in the May 16, 2003, issue of the journal Cell) their discovery of a plant gene for nitric oxide synthase, the enzyme that rapidly produces nitric oxide (NO) after infection. This is one of the earliest responses to pathogen attack.

"With nitric oxide synthase and now with SABP2, as well as other defense-signaling pathway components that have already or are sure to be discovered, we are beginning to see some effective and sustainable alternatives to pesticides," Klessig says, suggesting two possible strategies:

Genetic manipulation could enhance a crop plant's ability to make more of a scarce defense-signaling compound or a limiting receptor needed to transmit this signaling compound. Alternatively, crops could be treated with a functional mimic of the signaling compound itself when plant disease is anticipated.

"Either way, we are utilizing and enhancing a plant's own natural defenses," Klessig says. "That should be a better way, both because it will be much more difficult for pathogenic organisms to develop resistance and because we can avoid contaminating the environment."

He adds that an attack by a plant pathogen "marks the start of a war. If the plant can recognize the pathogen and activate its defense arsenal in time, the plant usually wins. But if the pathogen circumvents detection or the defenses themselves, the plant is in trouble. The more we learn about plant immune systems, the better are the chances we can help important crop plants win their war – without the collateral damage from chemical pesticides."

Klessig is president of BTI, an independent, not-for-profit organization located on the Cornell campus, and an adjunct professor of plant pathology; Kumar is a BTI research associate. The salicylic acid-binding protein research was supported by the National Science Foundation and by a plants and human health grant from the Triad Foundation.