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Transregional Collaborative Research Centre TRR 261

„Cellular Mechanisms of ANTIBIOTIC Action and Production“ (ANTIBIOTIC CellMAP)

Antibiotics - more than other therapeutic agents - have increased human life expectancy, but more and more pathogens are developing resistance against these former wonder drugs. New antibiotic classes are urgently needed but scarce in current development pipelines. Discovery strategies in the past decades have relied on high-throughput screening campaigns that have a very low success rate. There are still vast gaps in knowledge, both regarding the modes of action of antibiotics as well as the biology of bacterial cells exposed to these agents. Within the new TRR 261, an interdisciplinary team of scientists from the Universities of Tübingen and Bonn will work towards a better understanding of the fundamental processes of antibiotic action and production in bacterial cells.

Despite the fact that antibiotics have been used as therapies for decades, there is still need for fundamental research. It is often not understood what cascades of events occur within bacterial cells treated with antibiotics and which specific incident causes cell death. Many successful antibiotics attack multiple areas of the cellular metabolism. Antibiotic modes of action are the focus of project area A of the new TR-CRC. Here, the aim is to learn from the cellular mechanisms of potent antibiotics in order to better select and develop new compounds in the future.

About two thirds of all antibiotic classes successfully applied in therapy are natural products or derivatives thereof. Most of these compounds are synthesised by bacteria (the “producers”), which use the same molecular machineries in their cellular metabolism as the bacteria (the “targets”) against which these compounds are directed. In project area B the researchers will investigate antibiotic biosynthesis in such producing bacteria. They aim to understand how producer cells manage to conduct antibiotic biosynthesis, how they cope with the agents they produce, and what adaptations they need to make.

Unique to this collaborative research centre is the fact that the impact of antibiotics on “target cells” and “producer cells” are studied side-by-side within the same consortium. Notably, genetic analyses of bacterial producers show that the diversity of antibacterial agents synthesized in nature is much higher than what can be assessed in the laboratory. The scientists are convinced that greater knowledge concerning the physiology of the producer cells will allow them to stimulate the production of such agents that cannot yet be produced in the laboratory.