ArticleNature chemical biology2018
Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 71 citations in OpenAlex.
- The phenotypic landscape of the model firmicuteProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Applications of transposon-insertion sequencing for understanding bacterial physiology.Microbial genomics · 2026Review
- A broadly conserved gram-positive lipoprotein regulates cell elongation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mapping the genomic landscape of antibiotic susceptiblity in Escherichia coli.npj antimicrobials and resistance · 2026Article
- Hijacking the Electron Train: Menaquinone-Binding Antimicrobial Peptides.Chembiochem : a European journal of chemical biology · 2025Review
- Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus.Nature communications · 2025Article
- SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comprehensive genome analysis ofVeterinary world · 2025Article
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- Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution.mSystems · 2025Review
- Discovery of new AMR drugs targeting modulators of antimicrobial activity using in vivo silkworm screening systems.The Journal of antibiotics · 2025Review
- Correction of a widespread bias in pooled chemical genomics screens improves their interpretability.Molecular systems biology · 2024Article
- Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic.The Journal of antibiotics · 2024Review
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Sensing of Antibiotic-Bacteria Interactions.Antibiotics (Basel, Switzerland) · 2023Review
- A self-propagating, barcoded transposon system for the dynamic rewiring of genomic networks.Molecular systems biology · 2023Article
- Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2023Article
- Article
- Construction of high-density transposon mutant library of Staphylococcus aureus using bacteriophage ϕ11.Journal of microbiology (Seoul, Korea) · 2022Article
- Development of mass allelic exchange, a technique to enable sexual genetics inProceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivation mutants. We treated a Staphylococcus aureus transposon library containing 690,000 unique insertions with 32 antibiotics. Upregulation signatures identified from directional biases in insertions revealed known molecular targets and resistance mechanisms for the majority of these. Because single-gene upregulation does not always confer resistance, we used a complementary machine-learning approach to predict the mechanism from inactivation mutant fitness profiles. This approach suggested the cell wall precursor Lipid II as the molecular target of the lysocins, a mechanism we have confirmed. We conclude that docking to membrane-anchored Lipid II precedes the selective bacteriolysis that distinguishes these lytic natural products, showing the utility of our approach for nominating the antibiotic mechanism of action.
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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.