Secondary Metabolites in Amoebae-Bacteria Interactions (SMABI)

• Applicant: Professor Dr. Pierre Stallforth
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 388472265

Natural products are highly valuable sources of structurally diverse leads in the development of new therapeutic agents. Their areas of application include anti-infectives, immunomodulators, and anti-cancer agents to name but a few. The search for new bioactive compounds has prompted scientists to investigate untapped ecological niches. In particular, interacting microbial communities constitute a rich source of natural products. Microorganisms display an exquisite biosynthetic repertoire and they use natural products to communicate with other organisms, invade new habitats, or to acquire nutrients. Importantly, microbial defense strategies are often based on secreted secondary metabolites. For instance, bacteria are constantly exposed to a multitude of threats: bacteriophages can infect and kill bacteria; amoebae, nematodes, insects, amongst others can prey on prokaryotes, and competitor strains fight for the same resources. Consequently, bacteria have evolved highly effective defense mechanisms in order to survive in this battlefield. Killing and deterring antagonists are both powerful ways to thrive in this environment, hence bacteria display great diversity of toxins and antibiotics that selectively act on their enemies. Amoebae are some of the most voracious and ubiquitous of all bacterial predators, constantly depleting huge bacterial reservoirs. This predation puts both organisms under strong evolutionary selection pressure: the bacteria have evolved mechanisms to prevent grazing and the amoebae must counteract or surmount these mechanisms in order to survive. In this project, we investigate the interaction between bacterivorous amoebae and environmental bacteria. We are particularly interested in bacterial secondary metabolites that protect the bacteria from predation. This approach will enable the discovery of new - potentially anti-infective - secondary metabolites and advance our understanding of their biosyntheses, their structure activity relationship, and their biological/ecological functions.

• DFG Programme: Research Grants