Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Escherichia Coli (ncbitaxon:562)

SUBMITTER: Bernd Wollscheid

PROVIDER: MSV000084897 | MassIVE | Tue Feb 04 10:44:00 GMT 2020

SECONDARY ACCESSION(S): PXD010988

REPOSITORIES: MassIVE

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Thanatin targets the intermembrane protein complex required for lipopolysaccharide transport in <i>Escherichia coli</i>.

Vetterli Stefan U SU Zerbe Katja K Müller Maik M Urfer Matthias M Mondal Milon M Wang Shuang-Yan SY Moehle Kerstin K Zerbe Oliver O Vitale Alessandra A Pessi Gabriella G Eberl Leo L Wollscheid Bernd B Robinson John A JA

Science advances 20181114 11

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 are the proteins required for the biogenesis of the asymmetric Gram-negative bacterial outer membrane (OM). Seven Lpt proteins (LptA to LptG) associate in most Gram-negative bacteria to form a macromolecular complex spanning the entire envelope, which transports lipopolysaccharide (LPS) molecu ...[more]

PMID: 30443594

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