Swiss researchers have discovered antibiotically active chemical substances in the leaf of a common field weed.
Many of the antibiotics used today were developed from natural products made by bacteria themselves in order to ward off other bacteria. These products used to be sought and found primarily in soil.
Bacterial strains from the leaf surface of Arabidopsis thaliana, or thale cress, which grows in the wild in Eurasia and Africa, are being investigated as part of the National Research Programme “Antimicrobial Resistance” (NRP 72) funded by the Swiss National Science Foundation (SNSF).
The findings show that this microcosm, known as the phyllosphere and contains many still unknown natural products that could lead to new drugs.
Julia Vorholt of the Institute of Microbiology at ETH Zurich said because the phyllosphere is poor in nutrients, it gives rise to intense competitive pressure. “As a result, bacteria produce a diversity of substances that allow them to defend their habitat.”
That’s because despite the scarce food supply, the phyllosphere is populated by a large number of organisms. Vorholt and colleague Jörn Piel investigated more than 200 bacterial strains that occur in the widespread thale cresses.
Diverse antibiotic effects among bacteria
The team applied bioinformatics techniques to investigate gene clusters that are able to control the production of substances and could thus have an effect on other bacteria. To find out exactly what those effects are, the researchers ran parallel tests in the laboratory: they found 725 antibiotic interactions between various strains that prevent some of the bacteria from multiplying.
“The big question was obviously whether we had simply found natural products that are known from other habitats, or whether we had stumbled onto compounds with totally new characteristics,” Piel says. This has important implications for antibiotic research, which is seeking new antibiotics with mechanisms of action that are very different from those of today’s drugs and thus could overcome existing antibiotic resistance.
To determine whether they were dealing with new antibiotics, Vorholt and Piel had to study the chemical compositions in detail. They did this for gene clusters and compounds of a single strain of bacteria – Brevibacillus sp. Leaf182 – which was particularly productive. In so doing, they discovered several antibiotically active chemical substances. One of them, which the researchers named macrobrevin, exhibited a completely novel chemical structure.
“Now we need to clarify whether macrobrevin and other newly discovered substances are also effective against bacteria that cause disease in humans,” Piel says.
This is an exciting possibility, he says, but even more exciting is having shown that the relatively unexplored phyllosphere still contains many antibiotically active natural products to be discovered: “I have no doubt that this incredibly diverse ecosystem will provide medical science with many new approaches. Our findings confirm that it is worth expanding the search for antibiotics in nature.”
Around the world, an increasing array of pathogens are becoming resistant to today’s antibiotics. Because medicines are losing their effectiveness, once easy-to-treat infections are turning into deadly diseases. Switzerland’s six-year National Research Programme “Antimicrobial Resistance” (NRP 72) program investigates possible counteractions to this development, bringing together human and veterinary medical practitioners, biologists and environmental scientists to work in an interdisciplinary setting. The causes and effects of antibiotic resistance affect humans and farm animals as well as the environment, for instance through the transmission of resistant germs in wastewater.
The program, which began in 2015, has a budget of $US20 million and individual projects will be completed by the end of 2021.