New antibiotics

Pathogenic bacteria are increasingly resistant to today’s antibiotics. Professor Gilles van Wezel seeks new forms of antibiotics in good bacteria that live in the soil.

Sleeping genes

Many of today’s antibiotics are made from a special type of soil bacteria, the Streptomyces. These soil bacteria produce antibiotics that keep other – harmful – bacteria away. It was thought for decades that one of the Streptomyces, the Streptomyces Coelicolor, which has been studied intensively, could produce no more than four different antibiotics. However, it has since been found that these and other Streptomyces contain small groups of antibiotic-producing genes that had not previously been observed. Most of these genes appear to be dormant under laboratory conditions.

Molecular switches

Professor of Molecular Biotechnology Gilles van Wezel and his colleagues are looking for molecules that could serve as a switch to wake these sleeping genes and thus produce new types of antibiotics. Researchers screen libraries of chemical substances, for instance, in the hope that they will come across suitable molecules that could serve as a molecular switch to activate these genes.

Learning from nature

Van Wezel is also focusing his hunt on molecular switches in nature. He explains: ‘You can assume that there are conditions in the soil that cause the bacteria to produce these sleeping antibiotics. Otherwise these genes would not have been retained so long during evolution.’ He and researchers from Leiden and Wageningen did indeed discover that plants produce a compound that causes Streptomyces to produce antibiotics when another, harmful bacteria comes in the vicinity of the plant. The molecule that the plant produces is thus such a molecular switch. They are now further researching how this can be applied.

Technology with wide range of applications

The study of natural processes in Streptomyces has already resulted in a number of very promising new compounds for new antibiotics. Van Wezel believes that the technology could have a wide range of applications: ‘Streptomyces produce various different compounds to defend themselves from higher organisms like fungi and worms. These could form the basis of all sorts of drugs. Various anti-tumour drugs also come from Streptomyces, for instance. I think that you are much more likely to find completely new substances if you take this route than if you screen a general library of chemical substances. This approach works.’