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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1560235
This article is part of the Research Topic Emerging Antimicrobials: Sources, Mechanisms of Action, Spectrum of Activity, Combination Antimicrobial Therapy, and Resistance Mechanisms View all 21 articles
Antibiotic Fosmidomycin protects bacteria from cell wall perturbations by antagonizing oxidative damage-mediated cell lysis
Provisionally accepted- The University of Sydney, Darlington, Australia
Cell wall peptidoglycan is a defining component of bacterial cells, and its biosynthesis is a major target for medically important antibiotics. Recent studies have revealed that antibiotics can kill cells not just by their direct effects on wall synthesis but also by downstream perturbations of metabolic homeostasis, leading to oxidative damage mediated lysis. This work shows that isoprenoid biosynthesis has a crucial impact on the killing effects of various effectors of peptidoglycan inhibition in Bacillus subtilis. We show that intermediate levels of an antibiotic inhibitor of isoprenoid synthesis, fosmidomycin, confer resistance to lysis when peptidoglycan synthesis is perturbed, by limiting the availability of isoprenoid precursors for menaquinone, which is required for aerobic respiration. This work advances our understanding of the metabolic pathways involved in the bactericidal activity of important antibiotics.
Keywords: Bacillus subtilis, Cell Wall, isoprenoid, Oxidative damage, Fosfomycin, Fosmidomycin
Received: 14 Jan 2025; Accepted: 31 Mar 2025.
Copyright: © 2025 Kawai and Errington. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yoshikazu Kawai, The University of Sydney, Darlington, Australia
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