Abstract

Outer membrane biogenesis is a complex process for Gram-negative bacteria as the components are synthesized in the cytoplasm or at the inner membrane and then transported to the outer membrane. Stress pathways monitor and respond to problems encountered in assembling the outer membrane. The two-component system CpxAR was recently reported to be a stress pathway for transport of lipoproteins to the outer membrane, but it was unclear how this stress is sensed. May et al. [K. L. May, K. M. Lehman, A. M. Mitchell, and M. Grabowicz, mBio 10(3):e00618-19, 2019, https://doi.org/10.1128/mBio.00618-19] determined that an outer membrane lipoprotein, NlpE, is the sensor for lipoprotein biogenesis stress. The group demonstrated that CpxAR is activated by the N-terminal domain of NlpE when the lipoprotein accumulates at the inner membrane. Further, this work resolved a previously debated role for NlpE in sensing copper stress; copper was shown to inhibit acylation of lipoproteins, preventing them from being transported to the outer membrane.

Highlights

  • Gram-negative bacteria build a distinctive diderm cell envelope that provides unique advantageous properties, including particular resistance to permeation of toxic compounds and antibiotics [1]

  • The group demonstrated that CpxAR is activated by the N-terminal domain of NlpE when the lipoprotein accumulates at the inner membrane

  • Building an outer membrane (OM) comes with unique challenges, as the components are synthesized in the cytoplasm or at the inner membrane (IM) and transported across the IM and periplasm

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Summary

Introduction

Gram-negative bacteria build a distinctive diderm (two lipid bilayers) cell envelope that provides unique advantageous properties, including particular resistance to permeation of toxic compounds and antibiotics [1]. The group demonstrated that CpxAR is activated by the N-terminal domain of NlpE when the lipoprotein accumulates at the inner membrane.

Results
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