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 Nature paper describes a novel antibiotic class that targets the lipopolysaccharide (LPS) transport machinery in Gram-negative bacteria, specifically Acinetobacter. The antibiotics function by trapping a substrate-bound conformation of the LPS transporter, exploiting a composite binding site involving both the transporter and its LPS substrate. The work provides structural and mechanistic insights that could enable extension of this antibiotic class to other clinically significant Gram-negative pathogens.

UK applicability

As a fundamental microbiology study with no direct farming systems dimension, this research is relevant to the UK primarily in the context of antimicrobial stewardship and clinical infection control rather than agricultural practice or soil health.

Key measures

LPS transporter conformation, antibiotic binding kinetics, inhibition of LPS transport across bacterial transenvelope

Outcomes reported

The study identified a new class of antibiotics that inhibit lipopolysaccharide (LPS) transport in Gram-negative bacteria by trapping a substrate-bound conformation of the LPS transporter. Structural, biochemical and genetic approaches characterised this inhibitory mechanism and identified a druggable conformation of the Lpt transporter.

Theme
General food systems / other
Subject
Antimicrobial resistance
Study type
Research
Study design
Laboratory research (structural, biochemical and genetic approaches)
Source type
Peer-reviewed study
Status
Published
System type
Laboratory / in vitro
DOI
10.1038/s41586-023-06799-7
Catalogue ID
BFmou2m3wf-yav90b

Topic tags

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