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Lysophospholipid signaling coordinates outer membrane homeostasis in Escherichia coli
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Lysophospholipid signaling coordinates outer membrane homeostasis in Escherichia coli
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Journal Article
Lysophospholipid signaling coordinates outer membrane homeostasis in Escherichia coli
2026
Overview
The multilayered cell envelope of Gram-negative bacteria provides natural resistance to antibiotics. Understanding cell envelope synthesis and regulation is crucial for the identification of new antimicrobial targets and improved drug design. LpxC inhibitors, a new and promising class of antibiotics, impede function of the committed enzyme in lipopolysaccharide synthesis. Here, we characterize a new mechanism of resistance to the LpxC inhibitor PF-5081090, where the accumulation of lysophospholipids signals a reduction in cellular glycerophospholipid levels to repair outer membrane balance. This work proposes a new pathway to restore outer membrane asymmetry, which is a critical aspect of cell envelope integrity, and describes a role for lysophospholipids in bacterial cell signaling when lipopolysaccharide synthesis is disrupted.
Publisher
American Society for Microbiology,American Society for Microbiology (ASM)
Subject
/ Bacterial Outer Membrane - metabolism
/ Escherichia coli - drug effects
/ Escherichia coli - metabolism
/ Escherichia coli - physiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Lipopolysaccharides - biosynthesis
/ Lipopolysaccharides - metabolism
/ LplT
/ Lysophospholipids - metabolism
/ Microbial Physiology and Genetics
/ PldA
