The gain-of-function allele bamAE470K bypasses the essential requirement for BamD in β-barrel outer membrane protein assembly

Proceedings of the National Academy of Sciences of the United States of America
Elizabeth M HartThomas J Silhavy

Abstract

The outer membrane (OM) of gram-negative bacteria confers innate resistance to toxins and antibiotics. Integral β-barrel outer membrane proteins (OMPs) function to establish and maintain the selective permeability of the OM. OMPs are assembled into the OM by the β-barrel assembly machine (BAM), which is composed of one OMP-BamA-and four lipoproteins-BamB, C, D, and E. BamB, C, and E can be removed individually with only minor effects on barrier function; however, depletion of either BamA or BamD causes a global defect in OMP assembly and results in cell death. We have identified a gain-of-function mutation, bamA E470K , that bypasses the requirement for BamD. Although bamD::kan bamA E470K cells exhibit growth and OM barrier defects, they assemble OMPs with surprising robustness. Our results demonstrate that BamD does not play a catalytic role in OMP assembly, but rather functions to regulate the activity of BamA.

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Citations

Jul 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth M HartThomas J Silhavy
Aug 21, 2020·Journal of Bacteriology·Elizabeth M Hart, Thomas J Silhavy
Feb 10, 2021·Current Opinion in Microbiology·David Tomasek, Daniel Kahne
Apr 3, 2021·Drug Discovery Today·Scott S Walker, Todd A Black
May 29, 2021·FEMS Microbiology Letters·Maurice SteenhuisJoen Luirink
Aug 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Muralidhar TataAnna Konovalova

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