The cell envelope of diderm bacteria: a unified scaffold, not a stack of layers

The cell envelope of diderm (Gram-negative) bacteria is a defining structural and functional feature, ensuring mechanical integrity, supporting growth, and enabling adaptation to diverse environments. Traditionally viewed as a stack of discrete layers — the inner membrane, peptidoglycan, and outer membrane — this architecture is now recognized as a mechanically and physiologically integrated system. Recent advances have shown that envelope components are assembled and maintained in a coordinated manner, with physical and functional linkages bridging the different layers. In this review, we examine how these connections contribute to envelope biogenesis, homeostasis, and stress adaptation, using Escherichia coli as a reference model. We also discuss the evolutionary diversity of peptidoglycan-outer membrane attachment strategies across bacterial phyla, highlighting their conserved role in maintaining envelope cohesion. Together, these findings support a revised view of the envelope as a unified and dynamic structure, whose integrity depends on the coordinated activity of all its components.

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