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

Lookup NU author(s): Dr Yoshikazu Kawai, Maki Kawai, Dr Eilidh Mackenzie, Dr Yousef Dashti, Dr Bernhard Kepplinger, Dr Kevin Waldron, Professor Jeff Errington


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© 2023. Crown. 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.

Publication metadata

Author(s): Kawai Y, Kawai M, Mackenzie ES, Dashti Y, Kepplinger B, Waldron KJ, Errington J

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2023

Volume: 14

Issue: 1

Online publication date: 11/07/2023

Acceptance date: 20/06/2023

ISSN (electronic): 2041-1723

Publisher: Oxford University Press


DOI: 10.1038/s41467-023-39723-8

PubMed id: 37433811


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