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

Yoshikazu Kawai (), Maki Kawai, Eilidh Sohini Mackenzie, Yousef Dashti, Bernhard Kepplinger, Kevin John Waldron and Jeff Errington ()
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Yoshikazu Kawai: Newcastle University
Maki Kawai: Newcastle University
Eilidh Sohini Mackenzie: Newcastle University
Yousef Dashti: University of Sydney
Bernhard Kepplinger: University of Wrocław
Kevin John Waldron: Newcastle University
Jeff Errington: Newcastle University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39723-8

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