Project Area A

Cellular Mechanisms

Antibiotic activities in target cells

Projects included in Project Area A aim at a better understanding of antibiotic mechanisms of action. While some of the selected projects will address questions on antibiotics affecting novel targets (ClpP, the glmS riboswitch, sensor kinases), others strive to unravel the causes of enigmatic effects triggered by well-established, therapeutic antibiotics (beta-lactams, fosfomycin). A third group of compounds act at the validated peptidoglycan precursor lipid II, but can establish additional interactions with further bactoprenyl precursors or other membrane components, and we aim to shed light on the detrimental downstream consequences of these pleiotropic interactions. We are convinced that our proposed studies will provide explanations for puzzling observations made by us or by others concerning these antibiotics and such answers can only be found on the cellular level.

Project A01

Mechanism of prokaryotic specificity of ADEP antibiotics

Antibacterial acyldepsipeptides of the ADEP class have a unique bactericidal mechanism of action by targeting ClpP, the proteolytic core of the caseinolytic protease. ClpP is broadly conserved in bacteria, mitochondria, and chloroplasts. Although ADEP can kill intracellular bacteria and, thus, enters eukaryotic cells, and although it was shown to deregulate mitochondrial ClpP in vitro, ADEP is less toxic to eukaryotic than prokaryotic cells. In this project, the reason for this prokaryotic specificity is investigated.

Principal Investigator
Prof. Dr. Heike Brötz-Oesterhelt
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin
Mikrobielle Wirkstoffe
Eberhard Karls Universität Tübingen
Auf der Morgenstelle 28, 72076 Tübingen
+49 (0)7071 29-74706