A Natural Substitute for Pesticides

There can be no doubt that pesticides have been very useful since they first emerged. They protect our crops from all sorts of pests and enable them to grow better. But it has long been known that pesticides also cause harm. They make soils and waterways overly acidic and threaten the biodiversity of local plants and animals. Nevertheless, these chemical agents deliver high yields in agriculture, and many people have justified their use for this reason. However, these crop protection agents are not as all-powerful as you might think.

Even today, despite the use of pesticides and specialist growing methods, up to 40 percent of food crops around the world are still destroyed by pests or pathogens. This was the finding from research conducted by the Food and Agriculture Organization (FAO) of the United Nations. This problem is set to get significantly more acute in future. “In the next 10 years, it will no longer be possible to use most of the pesticides that are in use today,” says Cyril Zipfel, professor and head of the Molecular and Cellular Plant Physiology Laboratory at the University of Zurich. 

First, this is because more and more pesticides are being banned, or their use is being more strictly regulated because they can cause harm to natural flora and fauna. Second, the pathogens that the agents are designed to protect against are increasingly developing resistance to them – so spraying pesticides will no longer deliver any benefit. For example, the parasitic pathogens that cause potato powdery mildew have become partially resistant, as have fungal pathogens that infest soybeans and other crops. “That’s why we urgently need alternatives, ideally ones that don’t pollute the environment,” says Zipfel.

The plant immunologist is studying one such potential alternative – signaling peptides from the plant’s own immune system. He came across them while he was working with his team to study how plants respond to stress, for example to pathogens like bacteria and fungi or to heat and a shortage of water. Specifically, the researchers analyzed which plant genes are up-regulated in certain stressful situations. They identified that, among the thousands of activated genes, a particularly large number serve as a DNA template for these signaling peptides.

Although the peptides were already known to be vital plant hormones, Zipfel’s research now shows that these molecules are much more numerous and varied than previously assumed. And it also shows that they control a whole range of processes in different plants. “We now know that signaling peptides regulate every aspect of a plant’s life, from seed development and germination, growth and reproduction to how it responds to the environment,” says Zipfel.

The clever thing about this is that the peptides form a selection of possible switches that can be used to control plants – among other things, they could be made more resistant to diseases and pests. And all this without the use of any pesticides, as the approach is based purely on the natural means at the plants’ disposal. “But to do this, we first need to learn more about the signaling peptides to improve our understanding”, says the plant physiologist.

This is a complex undertaking. Even as the researchers attempted to identify as many of these peptides as possible in different plant species, they encountered challenges because the peptides have such varied structures. They can be of different sizes, with some consisting of more than a hundred amino acids and others just five of them. But then only part of the peptides is relevant to their biological function, and sometimes this is just a fraction of the whole peptide chain. This also means that at the DNA level, only some of their gene can actually be recognized as a pattern among the thousands of other plant genes. 

This is why Zipfel’s team will need to use and develop new computer-assisted methods to identify the signaling peptides. Then there’s the sheer quantity of these switch molecules: “If you look at the genetic material of the plants, every single one of them has the potential to produce hundreds to thousands of signaling peptides,” says Zipfel.

The researchers are now working on documenting the variety of signaling peptides and examining what effect they have in the plants. To do this, they have selected the genetic material from several hundred plants representing a cross-section of the family tree of all plant families, ranging from mosses and flowering plants to cereals and other crops. 

As a first step, the researchers will analyze these genomes using computer-assisted methods in order to identify the peptides and get an idea of their possible function. They will then need to develop methods to reproduce them in the lab. Finally, they will need appropriate tests that can be used to determine whether the peptides actually display the predicted biological activity and which other molecules and proteins they interact with. For example, the team is investigating which peptides bind to which receptors in the cell membranes. These receptors are essential for the plants’ information system and may trigger responses to different stimuli. 

The researchers have already identified a number of receptor/peptide pairs that interact in order to trigger a specific stress response. Among other tools, they are also using artificial intelligence to do this. More specifically, AI-assisted modeling to determine the structure of the peptides and get an indication of which receptor they bind to. They then confirm this prediction in the lab.

Zipfel’s team also observed that most of the peptides studied trigger similar characteristic responses in the cell at the beginning of their chain of action, within just a few milliseconds. They activate kinases, which are enzymes that in turn provide other proteins with a phosphate group and so trigger further signals within the cells. And they activate the transport of certain ions on the cell membranes, for example of calcium ions into the cells. “The concentration of calcium in plant cells is normally very low,” explains Zipfel. “The fact that it suddenly rises sends a signal that in turn initiates further signal processes.” As a result, the peptides trigger cascades of regulation signals.

What’s more, some of the peptide families also have a direct antimicrobial effect – and in theory, they are a potential substitute for antibiotics that are becoming less and less effective because of increasing resistance. But a great deal of research is still needed, says Zipfel. “The whole thing is a giant puzzle that we’re trying to piece together. We now know some of the pieces that go into the puzzle, and we’re working hard to find out how they fit together. Then there are also some pieces that we still need to identify.”

In the future, the team is keen to move even further away from typical laboratory model plants like the thale cress (Arabidopsis thaliana) and focus on commercial crops. Projects focusing on the potato, tomato and barley are already ongoing. The team’s findings suggest that the signaling peptides have diverged along plant phylogenetic trees. For example, there are peptides that are only found in tomatoes and related species, whereas others only exist in cereals.

One of the next challenges will be to find out how the peptides can be used in agricultural practice. “This will require close collaboration with chemists and agronomists,” says Zipfel. “It will be really exciting once we know the peptide families, including their effect, involved in the stress response for different crops.” They are precisely what could make plants more resistant to all kinds of threats – a natural substitute for pesticides.