Before the German dyestuffs firm of Bayer put aspirin on the marketin 1899, the age-old remedy for pain and fever was an herbal teabrewed from the bark of the willow tree _ botanical genus, Salix.

Hence the name of aspirin's active ingredient, salicylic acid. Butwhy would a common tree manufacture a universal nostrum againsthuman headaches and inflammation? To fight off viral, bacterial andfungal plant pests.

A transatlantic team of Ciba-Geigy Ltd. researchers, Swiss andAmerican, tell the story in today's issue of Science. Their article'stitle: "A central role of salicylic acid in plant disease resistance."

They report that tobacco (Nicotiana tabacum) and mouse-ear cress(Arabidopsis thaliana) plants, genetically engineered to express abacterial enzyme that degrades salicylic acid, incurred "increasedsusceptibility to viral, fungal and bacterial pathogens." Thebacterium Pseudomonas putida produces the enzyme, salicylatehydroxylase, for its own metabolic purposes. But laboratory plantsthat express the gene encoding that enzyme "cannot accumulatesalicylic acid, and thereby cannot induce systemic acquiredresistance," the researchers reported.

Those that can and do store up salicylic acid can deploy theirdefenses, for example, by producing antimicrobial proteins, orstrengthening their cell walls.

Systemic acquired resistance is among the modes by which plantsarm themselves against their natural microbial enemies. Another isgenetically determined resistance.

Molecular geneticist Terrence Delaney, first author of the Sciencepaper, explained to BioWorld Today how genetically determinedresistance works:

"It's often referred to as `gene-for-gene resistance,' " he said,"because plant and pathogen have genes that seem to match, so aspecific plant can recognize a specific pathogen. " This dating game,Delaney added, unleashes the plant's ability to accumulate thesalicylic acid resistance factor. The pathogens' sequences are calledavirulence genes, and the plants' corresponding sequences, resistancegenes.

This mutual recognition runs much more than species-deep. Itsspecificity varies by geographic host range. "For instance," Delaneysaid, "among our model A. thaliana species is an American isolate,and another that is native to Germany. We have races of downy-mildew fungus that will grow on the first but not the second, andvice versa."

Resistance Requires Salicylic Acid Accumulation

Avirulence genes are hot this year, Delaney observed. Many of themhave been cloned recently for the first time. "The point is," heunderscored, "as we demonstrate in this Science paper, thatgenetically determined resistance requires the plant to accumulatesalicylic acid, at least in our systems."

Ciba-Geigy scientists reported in the Aug. 6, 1993 Science that thesalicylic acid-dependent pathway induced systemic acquiredresistance. Extending its role to genetically determined resistance,Delaney pointed out, "is an important finding; the impact of today'spaper."

In an experiment reminiscent of preclinical challenges in mice,Delaney and his co-authors made A. thaliana plants transgenic forexpression of salicylate hydroxylase, the bacterial anti- salicylic acidenzyme. Then, before challenging these vulnerable plants with thefungal pathogen Peronospora parasitica, they "vaccinated" them witha synthetic analog of salicylic acid. This duly reversed the effect ofthe gene, and restored resistance to P. parasitica.

"This result," the Science paper stated, "demonstrates that the signaltransduction mechanism required for genetically determined diseaseresistance was intact in [the transgenic] plants, but failed to functionbecause of the action of salicylate hydroxylase."

Delaney observed, "Once we understand the mechanisms better atthe molecular level, they can give us rational approaches tomanipulate those expression pathways, through genetic engineeringor other methods. For example, salicylic acid itself can be applieddirectly to plants, and shown to induce resistance."

He does it by aerosol-misting his lab plants, but recalls thewidespread practice of dissolving an aspirin tablet into a vase of cutflowers, to keep the blooms fresh.

With an over-the-horizon eye to practical application, Delaneyadded, "This can obviously be extrapolated to chemicals that mightmimic that action."

N. tabacum is a favorite research model, as is A. thaliana. "We havediscovered very active promoters in our research," Delaney said,"that we feel might be very useful in producing specific biologicalsin tobacco, for example." He explained that certain of thepathogenesis-related plant genes have promoters that induce them toact, upon attack by pathogens. "We can consistently see 1,000-foldinduction in the tobacco gene," he revealed, or even, in someexperiments, 10,000-fold, in response to tobacco mosaic virusinfection."

Delaney allowed that this record increase over basal levels "couldhave a bearing on cultivation of high-value proteins in plants," buthe emphasized that "although such a practical spin-off might evolvefrom our basic research work, it is not central to it."

Plant pathologist Raymond Hammerschmidt at Michigan StateUniversity in East Lansing told BioWorld Today that "Those guysdown at Ciba in Triangle Park are more clearly showing the potentialthat the plants have to use their defense mechanisms. What they'redoing," he added, "parallels my own interests of the past couple ofdecades."

Hammerschmidt added, "The gene-for-gene concept gives breederssomething to work with in terms of breeding for these resistancegenes. The critical thing right there is to understand that theseresistance genes are there to help the plant identify the pathogen assomething it can resist. Also, how or why the pathogen is eventuallyable to overcome this resistance gene, by changing its ownavirulence gene product, which the plant would normally recognize."n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.