ArticleAntimicrobial agents and chemotherapy2010
Staphylococcus aureus TargetArray: comprehensive differential essential gene expression as a mechanistic tool to profile antibacterials.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Construction and application of the conditionally essential gene knockdown library inApplied and environmental microbiology · 2023Article
- High-throughput functional genomics: A (myco)bacterial perspective.Molecular microbiology · 2023Review
- Citrus Essential Oils: a Treasure Trove of Antibiofilm Agent.Applied biochemistry and biotechnology · 2022Review
- Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.Cell chemical biology · 2022Review
- Gradients in gene essentiality reshape antibacterial research.FEMS microbiology reviews · 2022Review
- Status quo of tet regulation in bacteria.Microbial biotechnology · 2022Review
- Predicting antimicrobial mechanism-of-action from transcriptomes: A generalizable explainable artificial intelligence approach.PLoS computational biology · 2021Article
- Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms.Nature chemistry · 2020Article
- Competitive Fitness of Essential Gene Knockdowns Reveals a Broad-Spectrum Antibacterial Inhibitor of the Cell Division Protein FtsZ.Antimicrobial agents and chemotherapy · 2018Article
- Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae.Nature communications · 2018Article
- Genomic and transcriptomic comparison between Staphylococcus aureus strains associated with high and low within herd prevalence of intra-mammary infection.BMC microbiology · 2017Article
- Competitive Growth Enhances Conditional Growth Mutant Sensitivity to Antibiotics and Exposes a Two-Component System as an Emerging Antibacterial Target in Burkholderia cenocepacia.Antimicrobial agents and chemotherapy · 2017Article
- Assessment of free fatty acids and cholesteryl esters delivered in liposomes as novel class of antibiotic.BMC research notes · 2016Article
- Article
- Genetic Approaches to Facilitate Antibacterial Drug Development.Cold Spring Harbor perspectives in medicine · 2015Review
- Article
- Genes contributing to Staphylococcus aureus fitness in abscess- and infection-related ecologies.mBio · 2014Article
- Effect of essential oils on pathogenic bacteria.Pharmaceuticals (Basel, Switzerland) · 2013Article
- Burkholderia cenocepacia conditional growth mutant library created by random promoter replacement of essential genes.MicrobiologyOpen · 2013Article
Corrections and comments
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Authors and funding
26 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The widespread emergence of antibiotic-resistant bacteria and a lack of new pharmaceutical development have catalyzed a need for new and innovative approaches for antibiotic drug discovery. One bottleneck in antibiotic discovery is the lack of a rapid and comprehensive method to identify compound mode of action (MOA). Since a hallmark of antibiotic action is as an inhibitor of essential cellular targets and processes, we identify a set of 308 essential genes in the clinically important pathogen Staphylococcus aureus. A total of 446 strains differentially expressing these genes were constructed in a comprehensive platform of sensitized and resistant strains. A subset of strains allows either target underexpression or target overexpression by heterologous promoter replacements with a suite of tetracycline-regulatable promoters. A further subset of 236 antisense RNA-expressing clones allows knockdown expression of cognate targets. Knockdown expression confers selective antibiotic hypersensitivity, while target overexpression confers resistance. The antisense strains were configured into a TargetArray in which pools of sensitized strains were challenged in fitness tests. A rapid detection method measures strain responses toward antibiotics. The TargetArray antibiotic fitness test results show mechanistically informative biological fingerprints that allow MOA elucidation.
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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.