ArticleProceedings of the National Academy of Sciences of the United States of America2016
Disruption of lipid homeostasis in the Gram-negative cell envelope activates a novel cell death pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 176 citations in OpenAlex.
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- Evaluation of arsenic-Tolerant plant growth-promoting rhizobacteria from Manipur for mitigating arsenic translocation and enhancing growth in rice (Oryza sativa).Scientific reports · 2025Article
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- TamL is a Key Player of the Outer Membrane Homeostasis in Bacteroidota.Journal of molecular biology · 2025Article
- Following phospholipid transfer through the OmpFProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Profiling Salmonella transcriptional dynamics during macrophage infection using a comprehensive reporter library.Nature microbiology · 2025Article
- Airborne Escherichia coli bacteria biosynthesize lipids in response to aerosolization stress.Scientific reports · 2025Article
- Recent advances in understanding of enterobacterial common antigen synthesis and regulation.Open biology · 2025Review
- The role of the essential GTPase ObgE in regulating lipopolysaccharide synthesis in Escherichia coli.Nature communications · 2024Article
- RNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence.Nature communications · 2024Article
- Investigating Lipid Transporter Protein and Lipid Interactions Using Variable Temperature Electrospray Ionization, Ultraviolet Photodissociation Mass Spectrometry, and Collision Cross Section Analysis.Analytical chemistry · 2024Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Gram-negative bacteria balance synthesis of the outer membrane (OM), cell wall, and cytoplasmic contents during growth via unknown mechanisms. Here, we show that a dominant mutation (designated mlaA*, maintenance of lipid asymmetry) that alters MlaA, a lipoprotein that removes phospholipids from the outer leaflet of the OM of Escherichia coli, increases OM permeability, lipopolysaccharide levels, drug sensitivity, and cell death in stationary phase. Surprisingly, single-cell imaging revealed that death occurs after protracted loss of OM material through vesiculation and blebbing at cell-division sites and compensatory shrinkage of the inner membrane, eventually resulting in rupture and slow leakage of cytoplasmic contents. The death of mlaA* cells was linked to fatty acid depletion and was not affected by membrane depolarization, suggesting that lipids flow from the inner membrane to the OM in an energy-independent manner. Suppressor analysis suggested that the dominant mlaA* mutation activates phospholipase A, resulting in increased levels of lipopolysaccharide and OM vesiculation that ultimately undermine the integrity of the cell envelope by depleting the inner membrane of phospholipids. This novel cell-death pathway suggests that balanced synthesis across both membranes is key to the mechanical integrity of the Gram-negative cell envelope.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.