ArticleACS chemical biology2016
Rapid Inhibition Profiling in Bacillus subtilis to Identify the Mechanism of Action of New Antimicrobials.
Article in ACS chemical biology, 2016. 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.
- Single-cell morphological responses as predictors of ciprofloxacin resistance inMicrobiology spectrum · 2026Article
- Temperature-dependent coliphage induces distinct temporal bacterial morphological dynamics during infection.Microbiology spectrum · 2026Article
- Deep learning-driven bacterial cytological profiling to determine antimicrobial mechanisms inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advancing antibiotic discovery with bacterial cytological profiling: a high-throughput solution to antimicrobial resistance.Frontiers in microbiology · 2025Review
- Perturbation-specific transcriptional mapping for unbiased target elucidation of antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Investigating the Molecular Interactions of Quinoline Derivatives for Antibacterial Activity Against Bacillus subtilis: Computational Biology and In Vitro Study Interpretations.Molecular biotechnology · 2024Article
- Unlocking the mechanism of action: a cost-effective flow cytometry approach for accelerating antimicrobial drug development.Microbiology spectrum · 2024Article
- Sensing of Antibiotic-Bacteria Interactions.Antibiotics (Basel, Switzerland) · 2023Review
- High-Resolution Bacterial Cytological Profiling Reveals Intrapopulation Morphological Variations upon Antibiotic Exposure.Antimicrobial agents and chemotherapy · 2023Article
- Article
- Cellular resource allocation strategies for cell size and shape control in bacteria.The FEBS journal · 2022Review
- Effects of antibiotics on bacterial cell morphology and their physiological origins.Biochemical Society transactions · 2022Review
- Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355.Scientific reports · 2022Article
- Article
- Review
- Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.Cell chemical biology · 2022Review
- Mansonone G and its derivatives exhibit membrane permeabilizing activities against bacteria.PloS one · 2022Article
- Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals.PloS one · 2022Article
- Bacterial Cytological Profiling Identifies Rhodanine-Containing PAINS Analogs as Specific Inhibitors ofJournal of bacteriology · 2021Article
- Bacterial cell shape control by nutrient-dependent synthesis of cell division inhibitors.Biophysical journal · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
Increasing antimicrobial resistance has become a major public health crisis. New antimicrobials with novel mechanisms of action (MOA) are desperately needed. We previously developed a method, bacterial cytological profiling (BCP), which utilizes fluorescence microscopy to rapidly identify the MOA of antimicrobial compounds. BCP is based upon our discovery that cells treated with antibiotics affecting different metabolic pathways generate different cytological signatures, providing quantitative information that can be used to determine a compound's MOA. Here, we describe a system, rapid inhibition profiling (RIP), for creating cytological profiles of new antibiotic targets for which there are currently no chemical inhibitors. RIP consists of the fast, inducible degradation of a target protein followed by BCP. We demonstrate that degrading essential proteins in the major metabolic pathways for DNA replication, transcription, fatty acid biosynthesis, and peptidoglycan biogenesis in Bacillus subtilis rapidly produces cytological profiles closely matching that of antimicrobials targeting the same pathways. Additionally, RIP and antibiotics targeting different steps in fatty acid biosynthesis can be differentiated from each other. We utilize RIP and BCP to show that the antibacterial MOA of four nonsteroidal anti-inflammatory antibiotics differs from that proposed based on in vitro data. RIP is a versatile method that will extend our knowledge of phenotypes associated with inactivating essential bacterial enzymes and thereby allow for screening for molecules that inhibit novel essential 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.