ArticleNature communications2019
Minimal exposure of lipid II cycle intermediates triggers cell wall antibiotic resistance.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed.
- Disruption of undecaprenyl phosphate recycling suppresses ampC beta-lactamase induction in Pseudomonas aeruginosa.PLoS pathogens · 2025Article
- Airborne Escherichia coli bacteria biosynthesize lipids in response to aerosolization stress.Scientific reports · 2025Article
- Constitutive activation of two-component systems reveals regulatory network interactions in Streptococcus agalactiae.Nature communications · 2024Article
- TheJournal of bacteriology · 2024Article
- Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa.Nature microbiology · 2024Article
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- The two-component system CroRS acts as a master regulator of cell envelope homeostasis to confer antimicrobial tolerance in the bacterial pathogen Enterococcus faecalis.Molecular microbiology · 2023Article
- Article
- Activation of ChvG-ChvI regulon by cell wall stress confers resistance to β-lactam antibiotics and initiates surface spreading in Agrobacterium tumefaciens.PLoS genetics · 2022Article
- Ag-Activated Metal-Organic Framework with Peroxidase-like Activity Synergistic AgNanomaterials (Basel, Switzerland) · 2022Article
- The Bacterial Cell Wall: From Lipid II Flipping to Polymerization.Chemical reviews · 2022Review
- Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.Nature communications · 2022Article
- Bacterial developmental checkpoint that directly monitors cell surface morphogenesis.Developmental cell · 2022Article
- Regulation of Resistance in Vancomycin-Resistant Enterococci: The VanRS Two-Component System.Microorganisms · 2021Review
- Tracking Colanic Acid Repeat Unit Formation from Stepwise Biosynthesis Inactivation inBiochemistry · 2021Article
- Resource sharing between central metabolism and cell envelope synthesis.Current opinion in microbiology · 2021Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- The Cell Envelope Stress Response ofAntibiotics (Basel, Switzerland) · 2020Article
- BceAB-Type Antibiotic Resistance Transporters Appear To Act by Target Protection of Cell Wall Synthesis.Antimicrobial agents and chemotherapy · 2020Article
- From Modules to Networks: a Systems-Level Analysis of the Bacitracin Stress Response in Bacillus subtilis.mSystems · 2020Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Cell wall antibiotics are crucial for combatting the emerging wave of resistant bacteria. Yet, our understanding of antibiotic action is limited, as many strains devoid of all resistance determinants display far higher antibiotic tolerance in vivo than suggested by the antibiotic-target binding affinity in vitro. To resolve this conflict, here we develop a comprehensive theory for the bacterial cell wall biosynthetic pathway and study its perturbation by antibiotics. We find that the closed-loop architecture of the lipid II cycle of wall biosynthesis features a highly asymmetric distribution of pathway intermediates, and show that antibiotic tolerance scales inversely with the abundance of the targeted pathway intermediate. We formalize this principle of minimal target exposure as intrinsic resistance mechanism and predict how cooperative drug-target interactions can mitigate resistance. The theory accurately predicts the in vivo efficacy for various cell wall antibiotics in different Gram-positive bacteria and contributes to a systems-level understanding of antibiotic action.
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Registered trials
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