Project description:Antimicrobial resistance is a leading mortality factor worldwide. Here we report the discovery of clovibactin, a new antibiotic, isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant Gram-positivebacterial pathogens without detectable resistance. Using biochemical assays,solid-state NMR, and atomic force microscopy, we dissect its mode of action. Clovibactin blocks cell wall synthesis by targeting pyrophosphate of multiple essential peptidoglycan precursors (C55PP, Lipid II, LipidWTA). Clovibactin uses anunusual hydrophobic interface to tightly wrap aroundpyrophosphate, butbypasses the variable structural elements of precursors, accounting for the lack of resistance. Selective and efficient target binding is achieved by the sequestration of precursors into supramolecular fibrils that only form on bacterial membranes that contain lipid-anchored pyrophosphate groups.Uncultured bacteria offer a rich reservoir of antibiotics with new mechanisms of action that could replenish the antimicrobial discovery pipeline.
Project description:This experiment aims on the identification of serine hydrolases from a complex thermophile community that live in a hot vent in Kamchatka Peninsula based on in vivo labelling with FP-alkyne directly in the hot spring and subsequent analysis using metagenomics/metaproteomics. To this end, sediment samples were collected and treated using the following three conditions. DMSO- treated control FP-alkyne labelled Samples for each condition were prepared in triplicate, resulting a total number of 6 samples per spring. Labelling was performed using 4 µM of the probe FP-alkyne and incubation for 2 h in the hot spring.
