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Mol Cell DOI:10.1016/j.molcel.2022.07.009

Reactive metabolic byproducts contribute to antibiotic lethality under anaerobic conditions.

Publication TypeJournal Article
Year of Publication2022
AuthorsWong, F, Stokes, JM, Bening, SC, Vidoudez, C, Trauger, SA, Collins, JJ
JournalMol Cell
Date Published2022 Aug 10
ISSN1097-4164
Abstract

Understanding how bactericidal antibiotics kill bacteria remains an open question. Previous work has proposed that primary drug-target corruption leads to increased energetic demands, resulting in the generation of reactive metabolic byproducts (RMBs), particularly reactive oxygen species, that contribute to antibiotic-induced cell death. Studies have challenged this hypothesis by pointing to antibiotic lethality under anaerobic conditions. Here, we show that treatment of Escherichia coli with bactericidal antibiotics under anaerobic conditions leads to changes in the intracellular concentrations of central carbon metabolites, as well as the production of RMBs, particularly reactive electrophilic species (RES). We show that antibiotic treatment results in DNA double-strand breaks and membrane damage and demonstrate that antibiotic lethality under anaerobic conditions can be decreased by RMB scavengers, which reduce RES accumulation and mitigate associated macromolecular damage. This work indicates that RMBs, generated in response to antibiotic-induced energetic demands, contribute in part to antibiotic lethality under anaerobic conditions.

DOI10.1016/j.molcel.2022.07.009
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35973427?dopt=Abstract

Alternate JournalMol Cell
PubMed ID35973427