ArticleNature chemical biology2011
High-frequency transposition for determining antibacterial mode of action.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Small-molecule inhibitors block NorA efflux by conformational trapping.Nature chemical biology · 2026Article
- A new regulator of the Staphylococcus aureus peptidoglycan hydrolase Sle1.PLoS genetics · 2025Article
- Article
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Transposon sequencing identifies genes impactingInfection and immunity · 2023Article
- A self-propagating, barcoded transposon system for the dynamic rewiring of genomic networks.Molecular systems biology · 2023Article
- Cell division protein FtsK coordinates bacterial chromosome segregation and daughter cell separation in Staphylococcus aureus.The EMBO journal · 2023Article
- Construction of high-density transposon mutant library of Staphylococcus aureus using bacteriophage ϕ11.Journal of microbiology (Seoul, Korea) · 2022Article
- Mutations inAntimicrobial agents and chemotherapy · 2022Article
- Gradients in gene essentiality reshape antibacterial research.FEMS microbiology reviews · 2022Review
- Improved Dynamic Range of a Rhamnose-Inducible Promoter for Gene Expression inApplied and environmental microbiology · 2021Article
- Next-generation microbiology: from comparative genomics to gene function.Genome biology · 2021Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives.Antibiotics (Basel, Switzerland) · 2021Review
- High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials.FEMS microbiology letters · 2020Article
- LipoproteinmBio · 2020Article
- Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies.Molecular cell · 2019Article
- Competitive Fitness of Essential Gene Knockdowns Reveals a Broad-Spectrum Antibacterial Inhibitor of the Cell Division Protein FtsZ.Antimicrobial agents and chemotherapy · 2018Article
- Inactivation of TCA cycle enhances Staphylococcus aureus persister cell formation in stationary phase.Scientific reports · 2018Article
- Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic.Nature chemical biology · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Connecting bacterial growth inhibitors to molecular targets at the whole-cell level is a major impediment to antibacterial development. Herein we report the design of a highly efficient and versatile bacteriophage-based mariner transposon delivery system in Staphylococcus aureus for determining inhibitor mode of action. Using bacteriophage-mediated delivery of concatameric minitransposon cassettes, we generated nonclonal transposant libraries with genome-wide insertion-site coverage in either laboratory or methicillin-resistant strain backgrounds and screened for drug resistance in situ on a single agar plate in one step. A gradient of gene-target expression levels, along with a correspondingly diverse assortment of drug-resistant phenotypes, was achieved by fitting the transposon cassette with a suite of outward-facing promoters. Using a panel of antibiotics, we demonstrate the ability to unveil not only an inhibitor's molecular target but also its route of cellular entry, efflux susceptibility and other off-target resistance mechanisms.
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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.