The AAA+ ATPase RavA and its binding partner ViaA modulate E. coli aminoglycoside sensitivity through interaction with the inner membrane
Jan Felix,
Ladislav Bumba,
Clarissa Liesche,
Angélique Fraudeau,
Fabrice Rébeillé,
Jessica Y. El Khoury,
Karine Huard,
Benoit Gallet,
Christine Moriscot,
Jean-Philippe Kleman,
Yoan Duhoo,
Matthew Jessop,
Eaazhisai Kandiah,
Frédéric Barras,
Juliette Jouhet and
Irina Gutsche ()
Additional contact information
Jan Felix: Univ Grenoble Alpes, CEA, CNRS, IBS
Ladislav Bumba: Univ Grenoble Alpes, CEA, CNRS, IBS
Clarissa Liesche: Univ Grenoble Alpes, CEA, CNRS, IBS
Angélique Fraudeau: Univ Grenoble Alpes, CEA, CNRS, IBS
Fabrice Rébeillé: Univ Grenoble Alpes, CEA, CNRS, INRAE, IRIG
Jessica Y. El Khoury: Institut Pasteur, Université de Paris, CNRS UMR6047, Stress Adaptation and Metabolism Unit, Department of Microbiology
Karine Huard: Univ Grenoble Alpes, CEA, CNRS, IBS
Benoit Gallet: Univ Grenoble Alpes, CEA, CNRS, IBS
Christine Moriscot: Univ Grenoble Alpes, CEA, CNRS, ISBG
Jean-Philippe Kleman: Univ Grenoble Alpes, CEA, CNRS, IBS
Yoan Duhoo: Univ Grenoble Alpes, CEA, CNRS, IBS
Matthew Jessop: Univ Grenoble Alpes, CEA, CNRS, IBS
Eaazhisai Kandiah: Univ Grenoble Alpes, CEA, CNRS, IBS
Frédéric Barras: Institut Pasteur, Université de Paris, CNRS UMR6047, Stress Adaptation and Metabolism Unit, Department of Microbiology
Juliette Jouhet: Univ Grenoble Alpes, CEA, CNRS, INRAE, IRIG
Irina Gutsche: Univ Grenoble Alpes, CEA, CNRS, IBS
Nature Communications, 2022, vol. 13, issue 1, 1-14
Abstract:
Abstract Enteric bacteria have to adapt to environmental stresses in the human gastrointestinal tract such as acid and nutrient stress, oxygen limitation and exposure to antibiotics. Membrane lipid composition has recently emerged as a key factor for stress adaptation. The E. coli ravA-viaA operon is essential for aminoglycoside bactericidal activity under anaerobiosis but its mechanism of action is unclear. Here we characterise the VWA domain-protein ViaA and its interaction with the AAA+ ATPase RavA, and find that both proteins localise at the inner cell membrane. We demonstrate that RavA and ViaA target specific phospholipids and subsequently identify their lipid-binding sites. We further show that mutations abolishing interaction with lipids restore induced changes in cell membrane morphology and lipid composition. Finally we reveal that these mutations render E. coli gentamicin-resistant under fumarate respiration conditions. Our work thus uncovers a ravA-viaA-based pathway which is mobilised in response to aminoglycosides under anaerobiosis and engaged in cell membrane regulation.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32992-9
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DOI: 10.1038/s41467-022-32992-9
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