MassIVE MSV000084897

Imported Reanalysis Dataset Public PXD010988

Thanatin Targets the Inter-Membrane Protein Complex Required for Lipopolysaccharide Transport in Escherichia coli

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Description

With the increasing resistance of many Gram-negative bacteria to existing classes of antibiotics, identifying new paradigms in antimicrobial discovery is an important research priority. Of special interest here are the proteins required for the biogenesis of the symmetric Gram-negative bacterial outer membrane. Seven Lpt proteins (LptA-G) associate in most Gram-negative bacteria to form a macromolecular complex spanning the entire envelope, which transports LPS molecules from their site of assembly at the inner membrane to the cell surface, powered by ATP hydrolysis in the cytoplasm. The periplasmic protein LptA comprises the protein bridge across the periplasm, which connects LptB2FGC at the inner membrane to LptD/E anchored in the outer membrane. We show here that the naturally occurring insect derived antimicrobial peptide thanatin targets LptA and LptD in the network of periplasmic protein-protein interactions required to assemble the Lpt complex, leading to inhibition ofLPS transport and OM biogenesis in Escherichia coli. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Gram-negative ESKAPE pathogens ; E.coli ; macrocyclic peptidomimetic antibiotics ; OMPTA (outer membrane-targeting antibiotics) ; Lpt complex ; photo crosslinking ; photoaffinity labeling ; interaction mapping ; DDA ; LC-MS/MS ; Thermo Q-Exactive Plus ; molecular mode of action ; MassIVE.quant reviewed - Gold

Contact

Principal Investigators:
(in alphabetical order) 		Bernd Wollscheid, Head of Proteomics Plattform Department of Health Sciences and Technology Institute of Molecular Systems Biology ETH Zurich Switzerland, N/A
Submitting User: ccms

Publications

Vetterli SU, Zerbe K, Müller M, Urfer M, Mondal M, Wang SY, Moehle K, Zerbe O, Vitale A, Pessi G, Eberl L, Wollscheid B, Robinson JA.
Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in Escherichia coli.
Sci Adv. 2018 Nov;4(11):eaau2634. Epub 2018 Nov 14.

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