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On the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis

Author

Listed:
  • Yoshikazu Kawai

    (Newcastle University
    University of Sydney)

  • Maki Kawai

    (Newcastle University
    University of Sydney)

  • Eilidh Sohini Mackenzie

    (Newcastle University)

  • Yousef Dashti

    (University of Sydney)

  • Bernhard Kepplinger

    (University of Wrocław)

  • Kevin John Waldron

    (Newcastle University
    Polish Academy of Sciences)

  • Jeff Errington

    (Newcastle University
    University of Sydney)

Abstract

Inhibition of bacterial cell wall synthesis by antibiotics such as β-lactams is thought to cause explosive lysis through loss of cell wall integrity. However, recent studies on a wide range of bacteria have suggested that these antibiotics also perturb central carbon metabolism, contributing to death via oxidative damage. Here, we genetically dissect this connection in Bacillus subtilis perturbed for cell wall synthesis, and identify key enzymatic steps in upstream and downstream pathways that stimulate the generation of reactive oxygen species through cellular respiration. Our results also reveal the critical role of iron homeostasis for the oxidative damage-mediated lethal effects. We show that protection of cells from oxygen radicals via a recently discovered siderophore-like compound uncouples changes in cell morphology normally associated with cell death, from lysis as usually judged by a phase pale microscopic appearance. Phase paling appears to be closely associated with lipid peroxidation.

Suggested Citation

  • Yoshikazu Kawai & Maki Kawai & Eilidh Sohini Mackenzie & Yousef Dashti & Bernhard Kepplinger & Kevin John Waldron & Jeff Errington, 2023. "On the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39723-8
    DOI: 10.1038/s41467-023-39723-8
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    References listed on IDEAS

    as
    1. M. Leaver & P. Domínguez-Cuevas & J. M. Coxhead & R. A. Daniel & J. Errington, 2009. "Life without a wall or division machine in Bacillus subtilis," Nature, Nature, vol. 457(7231), pages 849-853, February.
    2. Alexander J. Meeske & Eammon P. Riley & William P. Robins & Tsuyoshi Uehara & John J. Mekalanos & Daniel Kahne & Suzanne Walker & Andrew C. Kruse & Thomas G. Bernhardt & David Z. Rudner, 2016. "SEDS proteins are a widespread family of bacterial cell wall polymerases," Nature, Nature, vol. 537(7622), pages 634-638, September.
    3. M. Leaver & P. Domínguez-Cuevas & J. M. Coxhead & R. A. Daniel & J. Errington, 2009. "Erratum: Life without a wall or division machine in Bacillus subtilis," Nature, Nature, vol. 460(7254), pages 538-538, July.
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