Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function in Escherichia coli tol‐pal mutants. Issue 6 (10th September 2020)

• Record Type: Journal Article
• Authors: Jiang, Xiang'Er; Tan, Wee Boon; Shrivastava, Rahul; Seow, Deborah Chwee San; Chen, Swaine Lin; Guan, Xue Li; Chng, Shu‐Sin
• Is Part Of: Molecular microbiology. Volume 114:Issue 6(2020)
• Page Start: 991
• Page End: 1005
• Publication Date: 2020-09-10
• Subjects: ECA -- lipid homeostasis -- MPIase -- outer membrane barrier -- Tol‐Pal complex -- vancomycin resistance; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14590
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: The outer membrane (OM) is an essential component of the Gram‐negative bacterial envelope that protects the cells against external threats. To maintain a functional OM, cells require distinct mechanisms to ensure balance of proteins and lipids in the membrane. Mutations in OM biogenesis and/or homeostasis pathways often result in permeability defects, but how molecular changes in the OM affect barrier function is unclear. Here, we seek potential mechanism(s) that can alleviate permeability defects in Escherichia coli cells lacking the Tol‐Pal complex, which accumulate excess PLs in the OM. We identify mutations in enterobacterial common antigen (ECA) biosynthesis that re‐establish OM barrier function against large hydrophilic molecules, yet did not restore lipid homeostasis. Furthermore, we demonstrate that build‐up of biosynthetic intermediates, but not loss of ECA itself, contributes to the rescue. This suppression of OM phenotypes is unrelated to known effects that accumulation of ECA intermediates have on the cell wall. Finally, we reveal that an unusual diacylglycerol pyrophosphoryl‐linked lipid species also accumulates in ECA mutants, and might play a role in the rescue phenotype. Our work provides insights into how OM barrier function can be restored independent of lipid homeostasis, and highlights previously unappreciated effects of ECA‐related species in OM biology. Abstract : Escherichia coli strains lacking the Tol‐Pal complex exhibit outer membrane lipid dyshomeostasis, but how this molecular phenotype exactly translates to permeability defects is unclear. In this work, we discovered that the accumulation of intermediate species along the enterobacterial common antigen (ECA) pathway in tol‐pal mutants restores the outer membrane barrier function specifically against large hydrophilic molecules, yet does not restore balance in outer membrane lipid composition.