Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis

Abstract Gram-negative bacteria are defined by an outer membrane (OM) that contributes to envelope integrity and barrier function. Building this bilayer require proper assembly of lipopolysaccharides, proteins, and phospholipids, yet how the balance of these components is achieved is unclear. One sy...

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Main Authors: Wee Boon Tan, Shu-Sin Chng
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57630-y
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author Wee Boon Tan
Shu-Sin Chng
author_facet Wee Boon Tan
Shu-Sin Chng
author_sort Wee Boon Tan
collection DOAJ
description Abstract Gram-negative bacteria are defined by an outer membrane (OM) that contributes to envelope integrity and barrier function. Building this bilayer require proper assembly of lipopolysaccharides, proteins, and phospholipids, yet how the balance of these components is achieved is unclear. One system long known for ensuring OM stability is the Tol-Pal complex, which has been implicated in maintaining OM lipid homeostasis. However, assignment of Tol-Pal function has been challenging, owing to its septal localization and associated role(s) during division. Here, we uncouple the function of Tol-Pal in OM lipid homeostasis from its impact on cell division in Escherichia coli, by engineering a chimeric complex that loses septal enrichment. We demonstrate that this peripherally-localized Tol-Pal complex is fully capable of maintaining lipid balance in the OM, thus restoring OM integrity and barrier. Our work establishes the primary function of the Tol-Pal complex in OM lipid homeostasis, independent of its role during division.
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spelling doaj-art-7c97c4312e9346b2ae4c1bbea3e129872025-08-20T03:05:52ZengNature PortfolioNature Communications2041-17232025-03-0116111110.1038/s41467-025-57630-yPrimary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasisWee Boon Tan0Shu-Sin Chng1Department of Chemistry, National University ofDepartment of Chemistry, National University ofAbstract Gram-negative bacteria are defined by an outer membrane (OM) that contributes to envelope integrity and barrier function. Building this bilayer require proper assembly of lipopolysaccharides, proteins, and phospholipids, yet how the balance of these components is achieved is unclear. One system long known for ensuring OM stability is the Tol-Pal complex, which has been implicated in maintaining OM lipid homeostasis. However, assignment of Tol-Pal function has been challenging, owing to its septal localization and associated role(s) during division. Here, we uncouple the function of Tol-Pal in OM lipid homeostasis from its impact on cell division in Escherichia coli, by engineering a chimeric complex that loses septal enrichment. We demonstrate that this peripherally-localized Tol-Pal complex is fully capable of maintaining lipid balance in the OM, thus restoring OM integrity and barrier. Our work establishes the primary function of the Tol-Pal complex in OM lipid homeostasis, independent of its role during division.https://doi.org/10.1038/s41467-025-57630-y
spellingShingle Wee Boon Tan
Shu-Sin Chng
Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
Nature Communications
title Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
title_full Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
title_fullStr Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
title_full_unstemmed Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
title_short Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
title_sort primary role of the tol pal complex in bacterial outer membrane lipid homeostasis
url https://doi.org/10.1038/s41467-025-57630-y
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AT shusinchng primaryroleofthetolpalcomplexinbacterialoutermembranelipidhomeostasis