Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

A new antibiotic traps lipopolysaccharide in its intermembrane transporter

Karanbir S. Pahil, Morgan S. A. Gilman, Vadim Baidin, Thomas Clairfeuille, Patrizio Mattei, Christoph Bieniossek, Fabian Dey, Dieter Muri, Remo Baettig, Michael A. Lobritz, Kenneth A. Bradley, Andrew C. Kruse, Daniel Kahne

Nature · 2024

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Summary

This study describes a novel class of antibiotics that inhibit the lipopolysaccharide transport machinery in Gram-negative bacteria by recognising a composite binding site formed between the transporter protein and its LPS substrate, thereby stalling the transport process. Using structural, biochemical and genetic approaches, the researchers identified an unusual mechanism of lipid transport inhibition and revealed a previously undescribed druggable conformation of the Lpt transporter. The findings may enable extension of this antibiotic class to combat other clinically relevant Gram-negative pathogens.

Regional applicability

This fundamental microbiological research on antibiotic mechanisms has potential indirect relevance to UK antimicrobial resistance mitigation strategies and antibiotic stewardship in both human and veterinary medicine, though the work itself does not address agricultural or farming systems directly.

Key measures

Inhibitor binding site characterisation; transporter conformation states; LPS substrate interaction; bacterial cell viability assays; structural characterisation of antibiotic–LPS transporter interaction; genetic validation of inhibition mechanism

Outcomes reported

The study identified a novel antibiotic class that inhibits lipopolysaccharide (LPS) transport in Gram-negative bacteria by trapping a substrate-bound conformation of the LPS transporter. The research characterised the mechanism of action, the composite binding site between transporter and substrate, and the druggable conformational state of the Lpt transporter complex.

Theme
General food systems / other
Subject
Antimicrobial resistance
Study type
Research
Study design
Experimental structural biology study using cryo-electron microscopy, biochemical assays, and genetic analysis
Source type
Peer-reviewed study
Status
Published
System type
Laboratory / in vitro
DOI
10.1038/s41586-023-06799-7
Catalogue ID
BFmob79raq-cy3r9z

Topic tags

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