Research into new antibiotics: putting an end to antibiotic resistance

NEW ANTIBIOTICS FROM SEEDLINGS

Obtaining antibiotics from seedlings is an entirely new idea from food technologist Harry Gruppen, which could provide a solution to the serious problem of antibiotic resistance. Bacteria that cause infections are becoming increasingly resistant to several antibiotics. The development of resistance is due to the large-scale use of antibiotics. At the same time, very few new antibiotics have become available since 1960. New antibiotics are therefore desperately needed if we still want to be able to effectively fight infection.

Gruppen and his team have already demonstrated that germinated lupin seeds exposed to a mould produce multiple antibiotics to defend themselves. “We want to make the germination process and the isolation of the antibiotics from the plants more effective in a new project. The aim is to develop equipment that will produce seedlings containing active antibiotics on a large scale."
Companies and universities have searched for new antibiotics, but so far in vain. This is why Gruppen is now looking into germinating plants. Gruppen says: "The diversity of chemicals in plants is huge, and plant seedlings produce antibiotics naturally when they are exposed to stress. This represents a kind of hidden potential of substances which has hardly been worked on by researchers”

Importance of the research & Impact on society

Importance of the research
The World Health Organization (WHO) stated in 2014 that antibiotic resistance had reached an "alarming level". Doctors fear the bacterium MRSA, which is increasingly common in hospitals. Just one antibiotic is effective against this. The infection-causing bacteria Escherichia coli is dangerous because of its resistance to multiple antibiotics. In 2013, it was estimated that, in Europe, 25,000 deaths a year were caused by infections that could no longer be resisted with antibiotics. By 2050 there will be as many as 400,000 deaths if no new antibiotics are found, equating to 10 million at global level. Multi-drug resistant bacteria are especially dangerous for people with reduced immunity such as infants, the elderly, pregnant women and the sick. A breakthrough in finding new antibiotics is urgently needed.

Impact on society
Gruppen believes that not only lupin seedlings, but also seedlings of cereals and other legumes produce antibiotics under stress. When all the different seedlings produce different antibiotics on a larger scale, it can have a huge positive impact on healthcare and animal husbandry. Infections can be better controlled with so many new antibiotics available from plants. Food companies can use antibiotics from plants to prevent food spoilage. Consumers then get food with natural preservatives instead of synthetic preservatives. And for farmers, the production of stressed seeds can provide extra income.

History

The Wageningen researchers isolated five antibiotics from germinated lupin seeds that were exposed to mould. "We have demonstrated that these molecules kill bacteria" says Gruppen. “One of them, Wighteone, even appears to kill bacteria at the same concentration as the currently used antibiotics, namely at a few micrograms per millilitre.”

Initially, Gruppen’s team had about fifty seeds continually germinating in damp paper, just on a laboratory bench.  Since then, they have scaled up their process using a so-called malting machine in which four kilograms of seed can be germinated at once, under regulated conditions of  temperature, humidity and oxygen. This malting machine comes from the world of beer brewing. Malting machines are widely used by breweries for sprouting barley. Gruppen says: "That's the beauty of this approach. There is no need to develop equipment ourselves. We can just use beer-brewing equipment."

Research questions & Harry Gruppen's dream

Research questions
One of the research questions now is how to make the conditions optimal in the malting machine. Creating antibiotics, has to be triggered by mould, but the mould should not delay germination. Another research question concerns the type of antibiotics in the seedlings that most effectively tackle bacteria that cause infections. Gruppen says: "We also want to know why the plant antibiotics are effective. Once that is known, seedlings will be easier to screen for active substances and the process can be optimized more easily. Efficient production will be essential if we want to generate a breakthrough."

Harry Gruppen's dream
"My dream is that soon farmers around the world can grow crops from which seedlings can be cultivated. The resulting antibiotics, or the crushed seedlings, can then be used by food companies to preserve their products. The next step will be to make mixtures available to hospitals and veterinarians to fight infections in humans and animals. Mixtures are often more effective than individual antibiotics, because it is more difficult for bacteria to become resistant to these. Plants also produce mixtures of antibiotics. I also hope that the pharmaceutical industry can use our knowledge to develop synthetic antibiotics."

Strength of Wageningen University & Research

Wageningen University & Research hosts all the disciplines necessary to successfully address this multidisciplinary research. Food chemists identify what kinds of substances accumulate in stressed seedlings and what they do with bacteria. Plant physiologists determine the appropriate conditions in the malting machine so that optimum antibiotics are made. Food microbiologists test the effectiveness of the plant antibiotics as preservatives, and zoologists test the effects of the antibiotics on animals. All these disciplines have advanced equipment at their disposal.

Who are the partners?

The first partner in this research is the Radboud University in Nijmegen. This university is studying how the plant antibiotics effectively attack bacteria.

The second partner is the Erasmus Medical Centre in Rotterdam. This partner is testing the plant antibiotics in humans.

Budget

The research is divided into 12 doctoral studies. Two post-docs will coordinate and support the research. The study will also serve as a platform for a new MSc course in Chemistry and Inhibitory Mechanisms of Natural Antimicrobials for students.

A detailed budget will be sent on request.