Imaging Mass Spectrometer for Discovery/Visualization of Microbial Active Compounds
An increasing number of new and therapy-resistant pathogens poses growing challenges for our healthcare system and our society. In order to be able to react quickly against emerging infections with new or antibiotic-resistant bacteria and fungi, new and innovative therapeutic concepts and active substances are needed. Natural products play an important role as a source of new active ingredients. At the same time, they may also be involved in the development of many infectious diseases as mediators of biological communication. Leibniz-HKI is investigating the communication between microorganisms and the natural products involved in this communication in order to use this knowledge to develop innovative agents for the diagnosis and therapy of diseases. Thus, the molecular understanding of the role of natural products in infection processes can be used for the development of tailored therapies.
An innovative approach to discovering new natural products is the study of microbial communities. In nature, bacteria and fungi usually exist in complex societies that share habitats and interact with each other. These interactions, which can be pathogenic or mutualistic in nature, are often facilitated by substances produced by the microorganisms that act, for example, as signaling molecules, virulence factors, or growth factors. Such secondary metabolites represent ideal drug candidates due to their natural bioactivity. These highly potent substances are often produced only in very small quantities, so that their identification and characterization represent a major analytical challenge. A further problem arises from the fact that these substances are usually formed only under very specific conditions (usually leaning on the specific habitat of the producer), which are difficult to imitate in the laboratory. One way to address this challenge is to study the microorganisms in the natural context, e.g., in co-culture with microorganisms of the same habitat or directly in the biological matrix (e.g., in tissues of higher organisms). Mimicking the natural environment can induce the production of the specific metabolites so that they can be analyzed. However, this is only possible using modern analytical methods, such as imaging mass spectrometry. These techniques allow metabolites to be analyzed and visualized directly in the biological matrix (e.g., in tissue sections, in microbial co-cultures on agar plates, etc.).
To discover additional, highly potent and potentially pharmaceutically applicable compounds using this ecologically driven approach, we need a new mass spectrometer suitable for imaging. This instrument will replace our existing mass spectrometer, which is more than ten years old. New generation imaging-grade mass spectrometers show significant improvement in mass resolution, spatial resolution, measurement speed, and sensitivity, allowing us to detect compounds that are undetectable with our existing instrument. The transition from a nominal mass resolution in the existing instrument to a high resolution in the new instrument to be purchased allows the reliable calculation of sum formulas that cannot be realized with our existing instrument alone. This is the first and most important step in proving a compound. It allows dereplication with substance databases to avoid the costly and time consuming re-isolation of already known molecules.