Wild plants could be a treasure trove of new antibiotics for tackling the worldwide problem of antimicrobial resistance.
Researchers in Switzerland made this suggestion after discovering a compound with a new type of antibiotic activity on the leaf of the thale cress, a common weed.
Many of today’s antibiotics stem from natural compounds made by bacteria that live in soil. The bacteria produce them to defend against other microorganisms.
But the new study — now published in the journal Nature Microbiology — suggests that wild plants could also be a rich source of antibiotics.
The parts of plants that live above the ground are collectively known as the phyllosphere. The study focuses on a particular “ecosystem” of the phyllosphere — namely the leaf surface of a common weed.
Because this ecosystem lacks nutrients, there is “intense competitive pressure” among the many microorganisms that inhabit it, says co-senior study author Julia Vorholt, a professor in the Institute of Microbiology at ETH Zurich in Switzerland.
“As a result,” she explains, “bacteria produce a diversity of substances that allow them to defend their habitat.”
Antimicrobial resistance: A global threat
Antimicrobials are drugs that are designed to kill or stop the growth of microorganisms such as viruses, fungi, bacteria, yeasts, and parasitic worms. Antibiotics are antimicrobials that target bacteria, but the term is often used interchangeably with antimicrobials.
Antimicrobial resistance develops when microorganisms change in response to antimicrobial drugs and eventually cease to succumb to them. This makes it harder to treat the infections that they cause.
Our ability to cure even common infections is increasingly being undermined by the growing spread of new mechanisms of antimicrobial resistance. This is leading to longer recovery from illness, increased disability, and death.
A particular area of concern, for instance, is the treatment of tuberculosis (TB). The extensively drug-resistant form of the infectious disease has now been found in 105 countries and is resistant to “at least” four main anti-TB drugs.
Small plant with big potential
Prof. Vorholt and her colleagues investigated more than 200 species of bacteria that live on the leaves of Arabidopsis thaliana, a small wild plant with the common names thale cress and mouse-ear cress.
Arabidopsis is widely used as a model organism by scientists interested in the biology and genetics of flowering plants. This has led to a large library of genetic information that includes decoded genomes of the bacteria that colonize the plant’s leaf surfaces.
Until now, nobody had analyzed this data with a view to discovering “uncharacterized natural products” in the plant’s phyllosphere.
“We applied bioinformatics techniques,” says Prof. Vorholt, “to investigate gene clusters that are able to control the production of substances and could thus have an effect on other bacteria.”
After running several tests, the team found 725 molecular interactions between different strains of bacteria. The interactions were of bacteria targeting each other and, in some cases, they resulted in preventing their growth.
At this stage, however, it was not clear whether the compounds involved in the interactions were unique to this habitat or not. Also, did they possess completely novel antibiotic characteristics?
Finding substances with previously unknown antimicrobial mechanisms is a major goal in the fight against antimicrobial resistance.
Antibiotic with ‘unprecedented structure’
So, in the next stage of the study, the researchers examined the chemical makeup of the substances that they found. They focused on a “particularly productive” strain of bacteria called Brevibacillus sp. Leaf182.
An analysis of the compounds and “gene clusters” of the strain revealed a number of compounds with antibiotic powers. One in particular, that they called macrobrevin, had “an unprecedented natural product structure.”
“Now we need to clarify whether macrobrevin and other newly discovered substances are also effective against bacteria that cause disease in humans,” says co-senior study author Jörn Piel, who is also a professor in the Institute of Microbiology at ETH Zurich.
He adds that he and the rest of the team are excited by the fact that there could be many more naturally occurring antibiotics waiting to be found in the “relatively unexplored phyllosphere.”
“Our findings confirm that it is worth expanding the search for antibiotics in nature.”
Prof. Jörn Piel