Measurement technology and fluorescence spectrometers for research into co-culture processes

Shaking incubator, source: Dr. Lars Regestein / Leibniz-HKI

The global phenomenon of increasing resistance of pathogens to established active compounds currently poses serious challenges for the global community. There is an urgent need to develop innovative active substances and therapy concepts for the treatment of infections with multi-resistant germs and to bring them into application. One of the most important sources of new medicines are natural products synthesized by microorganisms. They are considered mediators of biological communication, but can also contribute to the development of infectious diseases. Thus, knowledge of microbial communication and the natural products involved opens up new paths for the development of effective active substances for the customized treatment of infections. Nowadays, however, it takes many times longer to discover new active substances than it did a few decades ago. Conventional antibiotics were usually discovered during the cultivation of individual microorganisms. The antimicrobial substances are primarily composed of compounds that ward off predators or food competitors. However, microorganisms are not found in isolation in nature and a pure culture produced in the laboratory is far removed from the conditions in the natural habitat. It can therefore be assumed that anti-infectives discovered to date only represent a small part of the biosynthetic potential.

A promising solution therefore seems to be the study of microorganisms in their natural context, for example in coexistence with other organisms of the same habitat. The so-called co-cultivation mimics natural conditions and can cause the production of previously unknown natural products, which are then analyzed and further researched. Thus, co-cultivation represents an important potential source of new antibiotics.

Microbial co-cultures and the associated processes are intensively researched in the Bio Pilot Plant at the Leibniz-HKI. The department has multiscale cultivation systems in which the results of basic research can be transferred to application-oriented processes.

Stable co-cultures of several microorganism species that do not dominate each other have so far been extremely difficult to produce under laboratory conditions. In practical terms, this means that it is not yet possible to optimize or even scale up such processes. However, both would be a breakthrough for the commercially and socially relevant use of the coexistence of microorganisms. Thus, in order to be able to establish stable co-cultures, measurement techniques and methods are required that make it possible to transfer results from basic research into application-oriented and scalable bioprocesses. For this purpose, measurement methods must be developed that record the growth of all microorganisms contained in a co-culture in real time. This information provides the basis for controlling, optimizing and scaling up a future co-culture process.

To enable us to transfer previously uncultivable microbial communities into biotechnological processes that generate new, ideally anti-infective agents, we need a new equipment infrastructure: new measurement technology for shaking incubators is required that can be connected to any known cultivation system. A new imaging 2D fluorescence spectrometer also makes it possible to monitor the formation of certain substances in the co-culture in real time. The new devices enable us to develop effective biotechnological processes. With their help, we will be able to provide sufficient quantities of new substances for development research at the Leibniz-HKI in the future. They also lay the foundation for later applications in the pharmaceutical industry.

Funding

The project, supported by the Free State of Thuringia, was co-financed by funds from the European Union as part of the European Regional Development Fund (ERDF).