Lipoprotein DolP supports proper folding of BamA in the bacterial outer membrane, promoting fitness upon envelope stress
- CNRS, France
- Institut Pasteur, France
Abstract
Integral outer membrane proteins (OMPs) are crucial for the maintenance of the proteobacterial envelope permeability barrier to some antibiotics and detergents. In Enterobacteria, envelope stress caused by unfolded OM proteins (OMPs) activates the sigmaE (σE) transcriptional response. σE upregulates OMP-biogenesis factors, including the b-barrel assembly machinery (BAM) that catalyzes OMP folding. Here we report that DolP (formerly YraP), a σE-upregulated and poorly understood OM lipoprotein, is crucial for fitness in cells that undergo envelope stress. We demonstrate that DolP interacts with the BAM complex by associating to OM-assembled BamA. We provide evidence that DolP is important for proper folding of BamA that overaccumulates in the OM, thus supporting OMP biogenesis and OM integrity. Notably, mid-cell recruitment of DolP had been linked to regulation of septal peptidoglycan remodelling by an unknown mechanism. We now reveal that, during envelope stress, DolP loses its association with the mid-cell, thereby suggesting a mechanistic link between envelope stress caused by impaired OMP biogenesis and the regulation of a late step of cell division.
Data availability
All data generated and analysed during this study are available in the manuscript and supporting files. Source data related to the CRISPRi screen are provided in the supporting files.
Article and author information
Author details
Luis Orenday-Tapia
Funding
Centre National de la Recherche Scientifique (ATIP-Avenir)
- Raffaele Ieva
Agence Nationale de la Recherche (ANR-10-INBS-08)
- Julien Marcoux
Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID)
- David Bikard
Fondation pour la Recherche Médicale (PostDoc Fellowship)
- David Ranava
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Ranava et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,753
- views
-
- 426
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Lipoprotein DolP supports proper folding of BamA in the bacterial outer membrane, promoting fitness upon envelope stress
eLife 10:e67817.
https://doi.org/10.7554/eLife.67817
Further reading
-
- Microbiology and Infectious Disease
A combination of imaging techniques reveals how herpes simplex virus type 1 assembles within infected cells, highlighting the roles of essential viral proteins in viral assembly and exit.
-
- Computational and Systems Biology
- Microbiology and Infectious Disease
Antimicrobial peptides (AMPs) are attractive candidates to combat antibiotic resistance for their capability to target biomembranes and restrict a wide range of pathogens. It is a daunting challenge to discover novel AMPs due to their sparse distributions in a vast peptide universe, especially for peptides that demonstrate potencies for both bacterial membranes and viral envelopes. Here, we establish a de novo AMP design framework by bridging a deep generative module and a graph-encoding activity regressor. The generative module learns hidden ‘grammars’ of AMP features and produces candidates sequentially pass antimicrobial predictor and antiviral classifiers. We discovered 16 bifunctional AMPs and experimentally validated their abilities to inhibit a spectrum of pathogens in vitro and in animal models. Notably, P076 is a highly potent bactericide with the minimal inhibitory concentration of 0.21 μM against multidrug-resistant Acinetobacter baumannii, while P002 broadly inhibits five enveloped viruses. Our study provides feasible means to uncover the sequences that simultaneously encode antimicrobial and antiviral activities, thus bolstering the function spectra of AMPs to combat a wide range of drug-resistant infections.
