ArticleMobile genetic elements2012
Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation.
Article in Mobile genetic elements, 2012. 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, 27 citations in OpenAlex.
- Article
- Article
- Signal peptidase SpsB coordinates staphylococcal cell cycle, surface protein septal trafficking and LTA synthesis.bioRxiv : the preprint server for biology · 2024Article
- Lipoteichoic acid biosynthesis bymBio · 2024Article
- Structure-Based Discovery of Lipoteichoic Acid Synthase Inhibitors.Journal of chemical information and modeling · 2022Article
- Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.Cell chemical biology · 2022Review
- Ftsh Sensitizes Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- The length of lipoteichoic acid polymers controlsJournal of bacteriology · 2020Article
- Antibacterial photosensitization through activation of coproporphyrinogen oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets.PLoS pathogens · 2016Article
- The inhibition of type I bacterial signal peptidase: Biological consequences and therapeutic potential.Bioorganic & medicinal chemistry letters · 2015Review
- A new platform for ultra-high density Staphylococcus aureus transposon libraries.BMC genomics · 2015Article
- A putative cro-like repressor contributes to arylomycin resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2015Article
- Systems-level antimicrobial drug and drug synergy discovery.Nature chemical biology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
Abstract
Determining the mechanism of action of bacterial growth inhibitors can be a formidable challenge in the progression of small molecules into antibacterial therapies. To help address this bottleneck, we have developed a robust transposon mutagenesis system using a suite of outward facing promoters in order to generate a comprehensive range of expression genotypes in Staphylococcus aureus from which to select defined compound-resistant transposon insertion mutants. Resistance stemming from either gene or operon over/under-expression, in addition to deletion, provides insight into multiple factors that contribute to a compound's observed activity, including means of cell envelope penetration and susceptibility to efflux. By profiling the entire resistome, the suitability of an antibacterial target itself is also evaluated, sometimes with unanticipated results. We herein show that for the staphylococcal signal peptidase (SpsB) inhibitors, modulating expression of lipoteichoic acid synthase (LtaS) confers up to a 100-fold increase in the minimal inhibitory concentration. As similarly efficient transposition systems are or will become established in other bacteria and cell types, we discuss the utility, limitations and future promise of Tnp mutagenesis for determining both a compound's mechanism of action and in the evaluation of novel targets.
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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.