N&H TOP LINE: Better ways of searching for antibiotics

By applying modern analytical methods, molecular structures can be linked to biological functions, and unique biological compounds can be created.

Antibiotic-resistant bacteria are a major problem worldwide. Molecular biologist Changsheng Wu at the Universiteit Leiden in the Netherlands explored innovative methods of developing new antibiotics more simply and more easily. He also discovered a new type of antibiotic.

More and more bacteria are threatening to become resistant to the antibiotics that are currently available. The problem is even so great that diseases like tuberculosis that had almost been eliminated are occurring again.

The results of Wu’s research, carried out at the Leiden's Institute of Biology under professor Gilles van Wezel and Dr. Young-Hae Choi, provide hope in the search for new antibiotics.

Wu showed, for example, that by applying modern analytical methods, molecular structures can be linked to biological and physical functions. Unique biological compounds can then be created in the laboratory. These new compounds may encompass new activities and sometimes completely new functions that do not occur in nature, and that can affect every aspect of life, the announcement said.

Furthermore, in developing antibiotics and other medical-natural applications, use is made of microorganisms belonging to the group of Actinomycetes (soil bacteria from which most of antibiotics originate).

Next-generation sequencing (NGS), the newest method of unravelling the genetics of organisms, shows that the potential of these Actinomycetes is far from being fully utilized. So-called dormant bacteria occur, which are bacteria that are not made under standard growing conditions and that are, therefore, never discovered by industry, the university said.

The big challenge now facing scientists is to activate these antibiotics — to awaken their potential — in order to be able to screen them and where possible apply them as medicines in the clinical environment.

New molecule Lugdunomycine. During his doctoral research, Wu discovered a number of different molecules with new chemical structures. Many of these were similar to already known molecules, but a pioneering discovery is that of Lugdunomycine: an antibiotic with antibacterial properties to combat gram-positive bacteria such as Bacillus subtilis and multi-resistant methicillin-resistant Staphylococcus aureus.

It is only very seldom that a molecule is discovered that in terms of structure is so different from known molecules, which emphasizes the importance of Wu's research, the university said.

These and other examples show that using a combination of methods can make it easier to discover new molecules. At the same time, it is possible to identify genetic information responsible for the biosynthesis route.

In his work, Wu combined different methods of cultivating microorganisms using NMR metabolomics (in simple terms, a method of detecting the intermediate and end-products of cultivating cells or tissues). His research showed that co-cultivation, developing two or more microorganisms in the same medium, in this case a fungus and a Streptomyces bacterium, can generate new compounds.

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