ArticleAntimicrobial agents and chemotherapy2017
Competitive Growth Enhances Conditional Growth Mutant Sensitivity to Antibiotics and Exposes a Two-Component System as an Emerging Antibacterial Target in Burkholderia cenocepacia.
Article in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Transcriptional Regulatory Systems in Pseudomonas: A Comparative Analysis of Helix-Turn-Helix Domains and Two-Component Signal Transduction Networks.International journal of molecular sciences · 2025Article
- Rationally designed pooled CRISPRi-seq uncovers an inhibitor of bacterial peptidyl-tRNA hydrolase.Cell reports · 2024Article
- The mechanism of action of auranofin analogs inMicrobiology spectrum · 2024Article
- Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium.Nature communications · 2023Article
- GSAMDA: a computational model for predicting potential microbe-drug associations based on graph attention network and sparse autoencoder.BMC bioinformatics · 2022Article
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- Improved Dynamic Range of a Rhamnose-Inducible Promoter for Gene Expression inApplied and environmental microbiology · 2021Article
- Multistep Signaling in Nature: A Close-Up ofInternational journal of molecular sciences · 2021Review
- Regulation of Virulence by Two-Component Systems in PathogenicInfection and immunity · 2020Review
- Competitive Fitness of Essential Gene Knockdowns Reveals a Broad-Spectrum Antibacterial Inhibitor of the Cell Division Protein FtsZ.Antimicrobial agents and chemotherapy · 2018Article
- Essential Two-Component Systems Regulating Cell Envelope Functions: Opportunities for Novel Antibiotic Therapies.The Journal of membrane biology · 2018Review
- Comparative analysis of the Burkholderia cenocepacia K56-2 essential genome reveals cell envelope functions that are uniquely required for survival in species of the genus Burkholderia.Microbial genomics · 2017Article
- Review
- Two-Component Signal Transduction Systems of Pathogenic Bacteria As Targets for Antimicrobial Therapy: An Overview.Frontiers in microbiology · 2017Review
- Review
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Authors and funding
8 authors.
Funding
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Abstract
Chemogenetic approaches to profile an antibiotic mode of action are based on detecting differential sensitivities of engineered bacterial strains in which the antibacterial target (usually encoded by an essential gene) or an associated process is regulated. We previously developed an essential-gene knockdown mutant library in the multidrug-resistant Burkholderia cenocepacia by transposon delivery of a rhamnose-inducible promoter. In this work, we used Illumina sequencing of multiplex-PCR-amplified transposon junctions to track individual mutants during pooled growth in the presence of antibiotics. We found that competition from nontarget mutants magnified the hypersensitivity of a clone underexpressing gyrB to novobiocin by 8-fold compared with hypersensitivity measured during clonal growth. Additional profiling of various antibiotics against a pilot library representing most categories of essential genes revealed a two-component system with unknown function, which, upon depletion of the response regulator, sensitized B. cenocepacia to novobiocin, ciprofloxacin, tetracycline, chloramphenicol, kanamycin, meropenem, and carbonyl cyanide 3-chlorophenylhydrazone, but not to colistin, hydrogen peroxide, and dimethyl sulfoxide. We named the gene cluster esaSR for enhanced sensitivity to antibiotics sensor and response regulator. Mutational analysis and efflux activity assays revealed that while esaS is not essential and is involved in antibiotic-induced efflux, esaR is an essential gene and regulates efflux independently of antibiotic-mediated induction. Furthermore, microscopic analysis of cells stained with propidium iodide provided evidence that depletion of EsaR has a profound effect on the integrity of cell membranes. In summary, we unraveled a previously uncharacterized two-component system that can be targeted to reduce antibiotic resistance in B. cenocepacia.
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