Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response

Abstract Bacteria use sophisticated acid stress response strategies to withstand fluctuating environmental pH, with enterobacterial inducible amino acid decarboxylases playing a major role. The lysine decarboxylase LdcI catalyses lysine-to-cadaverine conversion coupled to proton consumption and carb...

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Main Authors: Moritz A. Kirchner, Jessica El Khoury, Frédéric Barras, Jean-Philippe Kleman, Irina Gutsche
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08616-5
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author Moritz A. Kirchner
Jessica El Khoury
Frédéric Barras
Jean-Philippe Kleman
Irina Gutsche
author_facet Moritz A. Kirchner
Jessica El Khoury
Frédéric Barras
Jean-Philippe Kleman
Irina Gutsche
author_sort Moritz A. Kirchner
collection DOAJ
description Abstract Bacteria use sophisticated acid stress response strategies to withstand fluctuating environmental pH, with enterobacterial inducible amino acid decarboxylases playing a major role. The lysine decarboxylase LdcI catalyses lysine-to-cadaverine conversion coupled to proton consumption and carbon dioxide release, thereby buffering cytoplasmic and extracellular pH. Our previous studies showed that Escherichia coli LdcI forms intracellular patches under mild acid stress, and that purified LdcI polymerises into filaments at acidic pH. Here, we investigated the physiological relevance of LdcI filamentation using 3D super-resolution microscopy and an LdcI polymerisation-deficient E. coli mutant strain. We established a semi-automated workflow for intracellular cluster detection and quantitative analysis, and demonstrated predominantly peripheral clustering of LdcI. Disrupting LdcI polymerisation markedly reduced cluster size without significantly affecting localisation, suggesting that clustering is driven by filamentation. Growth and pH measurements revealed that the mutant exhibits reduced fitness and impaired extracellular buffering compared to the wild type, indicating that LdcI polymerisation enhances the E. coli capacity to counteract acid stress without affecting intracellular location of the enzyme. Our findings provide strong evidence that LdcI filamentation regulates acid stress response by spatially optimising enzymatic activity. More broadly, this work supports the functional significance of metabolic enzyme self-assembly in bacterial stress adaptation.
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spelling doaj-art-9622fc9b899b4e6e9264c2afc030324f2025-08-20T04:03:06ZengNature PortfolioCommunications Biology2399-36422025-08-01811910.1038/s42003-025-08616-5Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress responseMoritz A. Kirchner0Jessica El Khoury1Frédéric Barras2Jean-Philippe Kleman3Irina Gutsche4Institut de Biologie Structurale, CEA, CNRS UMR5075, Univ Grenoble AlpesDepartment of Microbiology, Institut Pasteur, Université de Paris, CNRS UMR6047, Stress Adaptation and Metabolism UnitDepartment of Microbiology, Institut Pasteur, Université de Paris, CNRS UMR6047, Stress Adaptation and Metabolism UnitInstitut de Biologie Structurale, CEA, CNRS UMR5075, Univ Grenoble AlpesInstitut de Biologie Structurale, CEA, CNRS UMR5075, Univ Grenoble AlpesAbstract Bacteria use sophisticated acid stress response strategies to withstand fluctuating environmental pH, with enterobacterial inducible amino acid decarboxylases playing a major role. The lysine decarboxylase LdcI catalyses lysine-to-cadaverine conversion coupled to proton consumption and carbon dioxide release, thereby buffering cytoplasmic and extracellular pH. Our previous studies showed that Escherichia coli LdcI forms intracellular patches under mild acid stress, and that purified LdcI polymerises into filaments at acidic pH. Here, we investigated the physiological relevance of LdcI filamentation using 3D super-resolution microscopy and an LdcI polymerisation-deficient E. coli mutant strain. We established a semi-automated workflow for intracellular cluster detection and quantitative analysis, and demonstrated predominantly peripheral clustering of LdcI. Disrupting LdcI polymerisation markedly reduced cluster size without significantly affecting localisation, suggesting that clustering is driven by filamentation. Growth and pH measurements revealed that the mutant exhibits reduced fitness and impaired extracellular buffering compared to the wild type, indicating that LdcI polymerisation enhances the E. coli capacity to counteract acid stress without affecting intracellular location of the enzyme. Our findings provide strong evidence that LdcI filamentation regulates acid stress response by spatially optimising enzymatic activity. More broadly, this work supports the functional significance of metabolic enzyme self-assembly in bacterial stress adaptation.https://doi.org/10.1038/s42003-025-08616-5
spellingShingle Moritz A. Kirchner
Jessica El Khoury
Frédéric Barras
Jean-Philippe Kleman
Irina Gutsche
Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
Communications Biology
title Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
title_full Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
title_fullStr Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
title_full_unstemmed Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
title_short Filamentation-driven peripheral clustering of the inducible lysine decarboxylase is crucial for E. coli acid stress response
title_sort filamentation driven peripheral clustering of the inducible lysine decarboxylase is crucial for e coli acid stress response
url https://doi.org/10.1038/s42003-025-08616-5
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