Plant compound may lead to new antibiotics

Scientists have discovered chemical substances antibiotic propertied on the leaf of a common field weed, paving the way for development of new drugs.

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.

Scientists from ETH Zurich in Switzerland are investigating bacterial strains from the leaf surface of Arabidopsis thaliana, or thale cress, which grows in the wild.

This microcosm, known as the phyllosphere, is poor in nutrients.

"That gives rise to intense competitive pressure. As a result, bacteria produce a diversity of substances that allow them to defend their habitat," said Julia Vorholt, from ETH Zurich.

Despite the scarce food supply, the phyllosphere is populated by a large number of organisms. Researchers investigated more than 200 bacterial strains that occur in the widespread thale cresses.

The genomes of the strains have been decoded, but have hardly been analysed in any targeted way until now.

"We 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," said Vorholt.

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," said Jorn Piel from ETH Zurich.

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, researchers 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.

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," said Piel.