Molecular biologist explores simple, innovative methods of developing new antibiotics

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

New functions

More and more bacteria are threatening to become resistant to the antibiotics currently available. The problem is even so great that diseases like tubercolosis that had almost been eliminated are occurring again. The results of Changsheng Wu's research, carried out at the Institute of Biology (IBL) 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 lab. These new compounds encompass new activities and sometimes completely new functions that do not occur in nature, and that can impact every aspect of human life.

Actinomycetes

In developing antibiotics and other medical-natural applications, use is made of micro-organisms belonging to the group of actinomycetes (soil bacteria from which most of our antibiotics come, Ed.). 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 utilised. So-called dormant bacteria occur, that is bacteria that are not made under standard growing conditions and that are therefore never discovered by industry. The big challenge now facing scientists is to activate these antibiotics (to awaken their potential, as it were), in order to be able to screen them and where possible apply them as medicines in the clinical environment.

The new molecule Lugdunomycine

During his PhD research, Changsheng 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 the multiresistant MRSA. It is only very seldom that a molecule is discovered that in terms of structure is so different from known molecules, which emphasises the importance of Changsheng Wu's research. 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.

Co-cultivation

In his work, Wu combined different methods of cultivating micro-organisms 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 micro-organisms in the same medium, in this case a fungus and a Streptomyces bacterium, can generate new compounds.

Multidisciplinary approach

Wu now advocates that scientists who are involved in the search for new antibiotics should have the necessary biological knowledge and practical genetic tools in their repertoire. Far-reaching multidiscipliniary cooperation between scientific experts, in his opinion, offers the best chance for making sure the search for new antibiotics is successful.

Source: Leiden University