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Peer-reviewedCC BY 4.0Proceedings of the National Academy of Sciences of the United States of America

Septin binding restricts Shigella growth and triggers intracellular tolerance

  • Gizem Özbaykal Güler1
  • Chen Zhang2
  • Dominik Brokatzky1
  • Rajdeep Das1
  • Richard Wheeler3
  • Ivo Gomperts Boneca3
  • Teresa Cortes4
  • Suliana Manley2
  • Serge Mostowy1
4 affiliations
  1. 1Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
  2. 2Laboratory of Experimental Biophysics, School of Basic Sciences, Institute of Physics, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
  3. 3Institut Pasteur, Université Paris Cité, CNRS Unité Mixe de Recherche 6047, INSERM U1306, Unité de Biologie et génétique de la paroi bactérienne, Paris F-75015, France
  4. 4Pathogen Gene Regulation Unit, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia 46010, Spain
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Abstract

Pathogen survival relies on their ability to adapt to changing environments, yet how intracellular bacteria tolerate cell-autonomous immunity remains unclear. Septins assemble into cage-like structures around cytoplasmic Shigella targeted by autophagy, but their antibacterial activity was unknown. Using advanced microscopy and cell-free reconstitution, we show that septins polymerize into circumferentially oriented filaments that inhibit bacterial growth. RNA-sequencing reveals that septin binding to Shigella upregulates type III secretion system (T3SS) effectors and triggers a stress response. Underlying this, septin-bound Shigella possess hyperpolarized membranes, but without lethally damaged cell envelope. We show that exposure to septin binding enhances the impact of the cell envelope-targeting antibiotic polymyxin B. During infection, T3SS effector OspC1 prevents septin recruitment, while stress-response regulator cspC protects against septin-mediated changes to membrane potential. Hence, septin binding is intrinsically antibacterial and is sensed by Shigella as a danger signal to promote mechanisms of intracellular tolerance.

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Cite

BibTeXRIS
BibTeX
@article{guler2026septin,
  title = {{Septin binding restricts Shigella growth and triggers intracellular tolerance}},
  author = {Gizem Özbaykal Güler and Chen Zhang and Dominik Brokatzky and Rajdeep Das and Richard Wheeler and Ivo Gomperts Boneca and Teresa Cortes and Suliana Manley and Serge Mostowy},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2529720123},
  url = {https://doi.org/10.1073/pnas.2529720123},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Septin binding restricts Shigella growth and triggers intracellular tolerance
AU  - Gizem Özbaykal Güler
AU  - Chen Zhang
AU  - Dominik Brokatzky
AU  - Rajdeep Das
AU  - Richard Wheeler
AU  - Ivo Gomperts Boneca
AU  - Teresa Cortes
AU  - Suliana Manley
AU  - Serge Mostowy
PY  - 2026
DA  - 2026/10/27
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2529720123
UR  - https://doi.org/10.1073/pnas.2529720123
AB  - Pathogen survival relies on their ability to adapt to changing environments, yet how intracellular bacteria tolerate cell-autonomous immunity remains unclear. Septins assemble into cage-like structures around cytoplasmic Shigella targeted by autophagy, but their antibacterial activity was unknown. Using advanced microscopy and cell-free reconstitution, we show that septins polymerize into circumferentially oriented filaments that inhibit bacterial growth. RNA-sequencing reveals that septin binding to Shigella upregulates type III secretion system (T3SS) effectors and triggers a stress response. Underlying this, septin-bound Shigella possess hyperpolarized membranes, but without lethally damaged cell envelope. We show that exposure to septin binding enhances the impact of the cell envelope-targeting antibiotic polymyxin B. During infection, T3SS effector OspC1 prevents septin recruitment, while stress-response regulator cspC protects against septin-mediated changes to membrane potential. Hence, septin binding is intrinsically antibacterial and is sensed by Shigella as a danger signal to promote mechanisms of intracellular tolerance.
SN  - 0027-8424
SN  - 1091-6490
ER  -