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

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

Nat Commun

Centre for Bacterial Cell Biology, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK.

Published: July 2023

AI Article Synopsis

  • Antibiotics like β-lactams disrupt bacterial cell wall synthesis, leading to cell lysis, but recent research shows they also interfere with central carbon metabolism, causing death through oxidative damage.
  • In this study, researchers examined the bacteria Bacillus subtilis and identified important enzymatic processes that result in the production of reactive oxygen species during respiration when cell wall synthesis is compromised.
  • The research highlights the importance of iron balance in causing oxidative damage and finds that a newly discovered compound can protect cells from oxidative stress, separating morphological changes from actual cell lysis.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336097PMC
http://dx.doi.org/10.1038/s41467-023-39723-8DOI Listing

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