Mechanism of outer membrane destabilization by global reduction of protein content

Irina V. Mikheyeva, Jiawei Sun, Kerwyn Casey Huang, Thomas J. Silhavy

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The outer membrane (OM) of Gram-negative bacteria such as Escherichia coli is an asymmetric bilayer with the glycolipid lipopolysaccharide (LPS) in the outer leaflet and glycerophospholipids in the inner. Nearly all integral OM proteins (OMPs) have a characteristic β-barrel fold and are assembled in the OM by the BAM complex, which contains one essential β-barrel protein (BamA), one essential lipoprotein (BamD), and three non-essential lipoproteins (BamBCE). A gain-of-function mutation in bamA enables survival in the absence of BamD, showing that the essential function of this protein is regulatory. Here, we demonstrate that the global reduction in OMPs caused by BamD loss weakens the OM, altering cell shape and causing OM rupture in spent medium. To fill the void created by OMP loss, phospholipids (PLs) flip into the outer leaflet. Under these conditions, mechanisms that remove PLs from the outer leaflet create tension between the OM leaflets, which contributes to membrane rupture. Rupture is prevented by suppressor mutations that release the tension by halting PL removal from the outer leaflet. However, these suppressors do not restore OM stiffness or normal cell shape, revealing a possible connection between OM stiffness and cell shape.

Original languageEnglish (US)
Article number5715
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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