Until 2016

We conduct research on new antimicrobial drugs

  • Antibiotics from predatory bacteria
  • Bacterial pests and their natural products
  • Genome mining-based drug discovery
  • Molecular principles of biosynthesis
  • Biotechnological production

Antimicrobial drugs are of major significance. In the field of medicine, they are indispensable for the treatment of life-threatening infections. In the food industry, they serve as preserving agents and in agriculture they are used for pest control. The majority of antimicrobial compounds that are in use today derive from natural products. The importance of these biogenous substances is due to their structural diversity, on the one hand, and to their optimized affinity to biological targets, on the other.

Owing to the increasing dissemination of resistant pathogens, there is a constant need of identifying novel antimicrobial drugs. Genomic analyses of bacteria and fungi confirmed that the potential of these organisms for the production of antibiotics is far from being exhausted. In fact, microbial genomes harbor numerous biosynthetic pathways that cannot be associated with known metabolites. Our research aims at exploiting these untapped resources. We are particularly interested in two groups of microorganisms:

1) Predatory bacteria are soil dwelling organisms that form swarms of cells in order to invade other bacteria as well as fungi. The concerted release of antibiotics contributes to the killing of the prey. From a pharmaceutical perspective, predatory bacteria are hence a promising source for finding new medicinal drugs.

2) Phytopathogenic bacteria have barely been explored with regard to their chemistry. However, genomic studies suggest a distinctive ability to natural product biosynthesis.

Head

Markus Nett

Drug discovery from predatory bacteria

Bacteria that band together in order to prey on other soil inhabitants are in the focus of our research. The formation of a pack enables these microorganisms to pursue a specific hunting strategy, which is beneficial  to all participants. While a single cell could not produce sufficient concentrations of an antibiotic to kill its prey, the concerted release of such compounds by an entire pack will have a profound effect. This form of collaboration which emerged in the course of evolution in several taxonomically distinct bacteria makes pack-forming bacteria a promising source for the finding of new, urgently needed antibiotics. Within this project, we isolate predatory bacteria from soil and freshwater habitats and we investigate them for the production of medicinally useful compounds. These studies are supported by the application of so-called genome mining strategies.

Novel bacterial siderophores

Siderophores are natural products, which safeguard the iron supply of microorganisms. These compounds have attracted a lot of interest due to their role as virulence factors for pathogenic bacteria and fungi, as well as potential carriers for antibiotics. In addition to their medical relevance, siderophores contribute to the structuring of microbial communities in the environment. By analyzing genomic sequence data, we identify bacteria that are capable of producing structurally unprecedented siderophores. We isolate and characterize these molecules and interrogate their significance in an ecological context.

Antibiotic biosynthesis

Siderophores are natural products, which safeguard the iron supply of microorganisms. These compounds have attracted a lot of interest due to their role as virulence factors for pathogenic bacteria and fungi, as well as potential carriers for antibiotics. In addition to their medical relevance, siderophores contribute to the structuring of microbial communities in the environment. By analyzing genomic sequence data, we identify bacteria that are capable of producing structurally unprecedented siderophores. We isolate and characterize these molecules and interrogate their significance in an ecological context.

Predation strategy of Cupriavidus necator

Cupriavidus necator is a predatory bacterium which can be found in many soil habitats. Preliminary studies showed that C. necator secretes a peptidic molecule with high affinity to copper(II) ions in the presence of prey organisms. The same compound was also proposed to play a major role in the interaction with the actinomycete Agromyces ramosus which is itself an aggressive microbial predator. Just like other actinomycetes, A. ramosus spreads via the formation of mycelia. Once a mycelial contact is established with potential prey cells, the actinomycete starts to secrete hydrolytic enzymes in order to consume these organisms. The same behaviour can be observed when A. ramosus encounters C. necator. In this particular case, however, the assaulted cells strike back. The counterattack coincides with the release of the copper-binding peptide, and it culminates in the complete killing of the actinomycete. The aim of this project is the identification and structural characterization of the copper-binding compound. Furthermore, we set out to unravel the factors, which induce the production of this compound.

Publications

Gross H, Kehraus S, Nett M, König GM, Beil W, Wright AD (2003) New cytotoxic cembrane based diterpenes from the soft corals Sarcophyton cherbonnieri and Nephthea sp. Org Biomol Chem 1(6), 944-949.