A chimeric Mla-Pqi lipid transport system is required for Brucella abortus survival in macrophages

Adélie Lannoy; Alexi Ronneau; Miguel Fernández-García; Marc Dieu; Patricia Renard; Antonia García Fernández; Raquel Condez-Alvarez; Xavier De Bolle

doi:10.1038/s44318-025-00511-3

A chimeric Mla-Pqi lipid transport system is required for Brucella abortus survival in macrophages

Adélie Lannoy, Alexi Ronneau, Miguel Fernández-García, Marc Dieu, Patricia Renard, Antonia García Fernández, Raquel Condez-Alvarez, Xavier De Bolle

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Abstract

The cell envelope of gram-negative bacteria is composed of an inner and an outer membrane. In Escherichia coli, several pathways mediate phospholipid transport between the two membranes, including the Mla (i.e., maintenance of lipid asymmetry) and Pqi (i.e., paraquat inducible) systems. Here, we identify and characterise in the intracellular pathogen Brucella abortus a complex named Mpc, which exhibits homology to both Mla and Pqi components. Mpc is required for bacterial growth under envelope stress conditions, and for survival within macrophages during the early stages of infection. Analyses of protein-protein interactions and structural predictions suggest that the Mpc complex bridges the two membranes of the bacterial cell envelope. Absence of this system results in altered lipid composition of the outer membrane vesicles, indicating that Mpc plays a role in lipid transport between the membranes. Our sequence comparisons reveal that Mpc is conserved across numerous species of Hyphomicrobiales. The discovery of this novel lipid-trafficking system expands our understanding of the diversity and evolution of lipid-transport mechanisms in diderm bacteria.

Original language	English
Pages (from-to)	5066-5085
Number of pages	20
Journal	The EMBO journal
Volume	44
Issue number	18
Early online date	13 Aug 2025
DOIs	https://doi.org/10.1038/s44318-025-00511-3
Publication status	Published - 15 Sept 2025

Funding

We thank M. Loperena Barber and R. Condez-Alvarez lab for their help in OMVs isolation and TLC assay; E. Carlier, M. Waroquier, C. Desy and F. Tilquin for their logistic support; C. Roomans and G. Lima Mendez for her help in the initial steps of protein structure prediction; and G. C. Demazy and S. Burteau for the MS sample preparation; P. Cherry and K. Poncin for the knowledge regarding pull-down; E. Barbieux for the experience of the Tn-seq assay; and staff at UNamur ( https://www.unamur.be/ ) for financial and logistical support. We thank the URBM researchers, JeanFrançois Collet (UCLouvain) and Basile Beaud Benyahia (Pasteur Institute, Paris), for stimulating discussions. The LABGeM (CEA/Genoscope and CNRS UMR8030), the France Génomique and French Bioinformatics Institute national infrastructures (funded as part of Investissement d’Avenir programme managed by Agence Nationale pour la Recherche, contracts ANR-10-INBS-09, ANR-11-INBS-0013 and ANR-21-ESRE-0048) are acknowledged for support within the MicroScope annotation platform. AL was supported by a FRIA (FNRS) PhD fellowship. This publication is supported by the Walloon Region as part of the funding for the FRFS-WELBIO strategic axis (X.1512.24). The work was also supported by PDR grants T.0058.20 and T.0068.24 from FRS-FNRS, as well as Concerted Research Action 17/22-087 and 22/27-128 from the Fédération Wallonie-Bruxelles. This research was carried out in the frame of project PID2023-146797OB-C31 financed by MCIN/AEI/10.1303910.13039/501100011033.

Funders	Funder number
UCLouvain
French Bioinformatics Institute national infrastructures
JeanFrançois Collet
Institut Pasteur
Fonds De La Recherche Scientifique - FNRS
Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
Basile Beaud Benyahia
PDR	T.0068.24, 22/27-128, T.0058.20, 17/22-087
Fédération Wallonie-Bruxelles	PID2023-146797OB-C31, MCIN/AEI/10.1303910.13039/501100011033
Agence Nationale de la Recherche	ANR-10-INBS-09, ANR-21-ESRE-0048, ANR-11-INBS-0013
Région Wallonne	X.1512.24

Keywords

Mla
Lipid Transport
Outer Membrane Biogenesis
Brucella
Pqi

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10.1038/s44318-025-00511-3Licence: CC BY

Lannoy et al 2025Final published version, 4.35 MB

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title = "A chimeric Mla-Pqi lipid transport system is required for Brucella abortus survival in macrophages",

abstract = "The cell envelope of gram-negative bacteria is composed of an inner and an outer membrane. In Escherichia coli, several pathways mediate phospholipid transport between the two membranes, including the Mla (i.e., maintenance of lipid asymmetry) and Pqi (i.e., paraquat inducible) systems. Here, we identify and characterise in the intracellular pathogen Brucella abortus a complex named Mpc, which exhibits homology to both Mla and Pqi components. Mpc is required for bacterial growth under envelope stress conditions, and for survival within macrophages during the early stages of infection. Analyses of protein-protein interactions and structural predictions suggest that the Mpc complex bridges the two membranes of the bacterial cell envelope. Absence of this system results in altered lipid composition of the outer membrane vesicles, indicating that Mpc plays a role in lipid transport between the membranes. Our sequence comparisons reveal that Mpc is conserved across numerous species of Hyphomicrobiales. The discovery of this novel lipid-trafficking system expands our understanding of the diversity and evolution of lipid-transport mechanisms in diderm bacteria.",

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AU - Lannoy, Adélie

AU - Ronneau, Alexi

AU - Fernández-García, Miguel

AU - Dieu, Marc

AU - Renard, Patricia

AU - García Fernández, Antonia

AU - Condez-Alvarez, Raquel

AU - De Bolle, Xavier

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/9/15

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N2 - The cell envelope of gram-negative bacteria is composed of an inner and an outer membrane. In Escherichia coli, several pathways mediate phospholipid transport between the two membranes, including the Mla (i.e., maintenance of lipid asymmetry) and Pqi (i.e., paraquat inducible) systems. Here, we identify and characterise in the intracellular pathogen Brucella abortus a complex named Mpc, which exhibits homology to both Mla and Pqi components. Mpc is required for bacterial growth under envelope stress conditions, and for survival within macrophages during the early stages of infection. Analyses of protein-protein interactions and structural predictions suggest that the Mpc complex bridges the two membranes of the bacterial cell envelope. Absence of this system results in altered lipid composition of the outer membrane vesicles, indicating that Mpc plays a role in lipid transport between the membranes. Our sequence comparisons reveal that Mpc is conserved across numerous species of Hyphomicrobiales. The discovery of this novel lipid-trafficking system expands our understanding of the diversity and evolution of lipid-transport mechanisms in diderm bacteria.

AB - The cell envelope of gram-negative bacteria is composed of an inner and an outer membrane. In Escherichia coli, several pathways mediate phospholipid transport between the two membranes, including the Mla (i.e., maintenance of lipid asymmetry) and Pqi (i.e., paraquat inducible) systems. Here, we identify and characterise in the intracellular pathogen Brucella abortus a complex named Mpc, which exhibits homology to both Mla and Pqi components. Mpc is required for bacterial growth under envelope stress conditions, and for survival within macrophages during the early stages of infection. Analyses of protein-protein interactions and structural predictions suggest that the Mpc complex bridges the two membranes of the bacterial cell envelope. Absence of this system results in altered lipid composition of the outer membrane vesicles, indicating that Mpc plays a role in lipid transport between the membranes. Our sequence comparisons reveal that Mpc is conserved across numerous species of Hyphomicrobiales. The discovery of this novel lipid-trafficking system expands our understanding of the diversity and evolution of lipid-transport mechanisms in diderm bacteria.

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A chimeric Mla-Pqi lipid transport system is required for Brucella abortus survival in macrophages

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A chimeric Mla-Pqi lipid transport system is required for Brucella abortus survival in macrophages

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

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Biological Security Laboratory Level 3 (BL3)

Mass Spectrometry Service

Cite this