ArticleEMBO reports2021
A multifaceted cellular damage repair and prevention pathway promotes high-level tolerance to β-lactam antibiotics.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Peptidoglycan Remodeling in Gram-Negative Bacteria: From Stress Adaptation to Antibiotic Tolerance and Therapeutic Targeting.Antibiotics (Basel, Switzerland) · 2026Review
- Synergistic action of peptidoglycan and teichoic acid synthesis inhibitors leads to cell death by oxidative damage.Communications biology · 2026Article
- Multilevel Regulation of Peptidoglycan Dynamics in Bacteria: From Molecular Mechanisms to Applied Perspectives.Biomolecules · 2026Review
- Global response to antibiotic exposure reveals a critical role for nucleotide metabolism in high-level β-lactam tolerance.npj antimicrobials and resistance · 2026Article
- Prevalence and mechanisms of high-level carbapenem antibiotic tolerance in clinical isolates of Klebsiella pneumoniae.PLoS pathogens · 2026Article
- Global response to antibiotic exposure uncovers a critical role for nucleotide metabolism in high-level β-lactam tolerance.Research square · 2025Article
- Characterization and Anti-Inflammatory Effects ofMicroorganisms · 2025Article
- Antibiotic fosmidomycin protects bacteria from cell wall perturbations by antagonizing oxidative damage-mediated cell lysis.Frontiers in microbiology · 2025Article
- Pleiotropic cellular responses underlying antibiotic tolerance inFrontiers in microbiology · 2024Article
- Mechanical stimuli activate gene expression via a cell envelope stress sensing pathway.Scientific reports · 2023Article
- On the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis.Nature communications · 2023Article
- Sporadic type VI secretion in seventh pandemicMicrobiology (Reading, England) · 2023Article
- The Rvv two-component regulatory system regulates biofilm formation and colonization in Vibrio cholerae.PLoS pathogens · 2023Article
- Disrupting Central Carbon Metabolism Increases β-Lactam Antibiotic Susceptibility in Vibrio cholerae.Journal of bacteriology · 2023Article
- Bacterial metabolism and susceptibility to cell wall-active antibiotics.Advances in microbial physiology · 2023Review
- Downregulation of Nrf2 in the Hippocampus Contributes to Postoperative Cognitive Dysfunction in Aged Rats by Sensitizing Oxidative Stress and Neuroinflammation.Oxidative medicine and cellular longevity · 2023Article
- Article
- The Bacterial Cell Wall: From Lipid II Flipping to Polymerization.Chemical reviews · 2022Review
- High-level carbapenem tolerance requires antibiotic-induced outer membrane modifications.PLoS pathogens · 2022Article
- Bacterial two-component systems as sensors for synthetic biology applications.Current opinion in systems biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Bactericidal antibiotics are powerful agents due to their ability to convert essential bacterial functions into lethal processes. However, many important bacterial pathogens are remarkably tolerant against bactericidal antibiotics due to inducible damage repair responses. The cell wall damage response two-component system VxrAB of the gastrointestinal pathogen Vibrio cholerae promotes high-level β-lactam tolerance and controls a gene network encoding highly diverse functions, including negative control over multiple iron uptake systems. How this system contributes to tolerance is poorly understood. Here, we show that β-lactam antibiotics cause an increase in intracellular free iron levels and collateral oxidative damage, which is exacerbated in the ∆vxrAB mutant. Mutating major iron uptake systems dramatically increases ∆vxrAB tolerance to β-lactams. We propose that VxrAB reduces antibiotic-induced toxic iron and concomitant metabolic perturbations by downregulating iron uptake transporters and show that iron sequestration enhances tolerance against β-lactam therapy in a mouse model of cholera infection. Our results suggest that a microorganism's ability to counteract diverse antibiotic-induced stresses promotes high-level antibiotic tolerance and highlights the complex secondary responses elicited by antibiotics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.