ArticleThe Journal of antibiotics2016
Application of bacterial cytological profiling to crude natural product extracts reveals the antibacterial arsenal of Bacillus subtilis.
Article in The Journal of antibiotics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
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- Poly(imidazolium ester) antibiotic forms intracellular polymer-nucleic acid biomolecular condensates and fight drug-resistant bacteria.Nature communications · 2025Article
- Deep learning-driven bacterial cytological profiling to determine antimicrobial mechanisms inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolic engineering approaches for the biosynthesis of antibiotics.Microbial cell factories · 2025Review
- Advancing antibiotic discovery with bacterial cytological profiling: a high-throughput solution to antimicrobial resistance.Frontiers in microbiology · 2025Review
- Combining machine learning with high-content imaging to infer ciprofloxacin susceptibility in isolates of Salmonella Typhimurium.Nature communications · 2024Article
- Sensing of Antibiotic-Bacteria Interactions.Antibiotics (Basel, Switzerland) · 2023Review
- High-throughput functional genomics: A (myco)bacterial perspective.Molecular microbiology · 2023Review
- High-Resolution Bacterial Cytological Profiling Reveals Intrapopulation Morphological Variations upon Antibiotic Exposure.Antimicrobial agents and chemotherapy · 2023Article
- The genome ofFrontiers in microbiology · 2023Article
- Microscopy-Based Multiwell Assay to Characterize Disturbed Bacterial Morphogenesis Upon Antibiotic Action.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The chemical ecology of the fungus-farming termite symbiosis.Natural product reports · 2022Review
- AntimicrobialAntibiotics (Basel, Switzerland) · 2022Review
- 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
- Mining genomes to illuminate the specialized chemistry of life.Nature reviews. Genetics · 2021Review
- Article
- Characterization and Quantitative Determination of a Diverse Group of Bacillus subtilis subsp. subtilis NCIB 3610 Antibacterial Peptides.Probiotics and antimicrobial proteins · 2021Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Although most clinically used antibiotics are derived from natural products, identifying new antibacterial molecules from natural product extracts is difficult due to the complexity of these extracts and the limited tools to correlate biological activity with specific molecules. Here, we show that bacterial cytological profiling (BCP) provides a rapid method for mechanism of action determination on plates and in complex natural product extracts and for activity-guided purification. We prepared an extract from Bacillus subtilis 3610 that killed the Escherichia coli lptD mutant and used BCP to observe two types of bioactivities in the unfractionated extract: inhibition of translation and permeablization of the cytoplasmic membrane. We used BCP to guide purification of the molecules responsible for each activity, identifying the translation inhibitors bacillaene and bacillaene B (glycosylated bacillaene) and demonstrating that two molecules contribute to cell permeabilitization, the bacteriocin subtilosin and the cyclic peptide sporulation killing factor. Our results suggest that bacillaene mediates translational arrest, and show that bacillaene B has a minimum inhibitory concentration 10 × higher than unmodified bacillaene. Finally, we show that BCP can be used to screen strains on an agar plate without the need for extract preparation, greatly saving time and improving throughput. Thus, BCP simplifies the isolation of novel natural products, by identifying strains, crude extracts and fractions with interesting bioactivities even when multiple activities are present, allowing investigators to focus labor-intensive steps on those with desired activities.
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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.