ArticleAntimicrobial agents and chemotherapy2000
Identification and analysis of bacterial protein secretion inhibitors utilizing a SecA-LacZ reporter fusion system.
Article in Antimicrobial agents and chemotherapy, 2000. 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.
- Whole Cell Luminescence-Based Screen for Inhibitors of the Bacterial Sec Machinery.Biochemistry · 2024Article
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- Secretome Dynamics in a Gram-Positive Bacterial Model.Molecular & cellular proteomics : MCP · 2019Article
- The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics.Annals of the New York Academy of Sciences · 2019Review
- SecA inhibitors as potential antimicrobial agents: differential actions on SecA-only and SecA-SecYEG protein-conducting channels.FEMS microbiology letters · 2018Review
- Identification of small-molecule inhibitors against SecA by structure-based virtual ligand screening.The Journal of antibiotics · 2015Article
- SecA: a potential antimicrobial target.Future medicinal chemistry · 2015Review
- Interactions between an anti-sigma protein and two sigma factors that regulate the pyoverdine signaling pathway in Pseudomonas aeruginosa.BMC microbiology · 2014Article
- Identification of a small-molecule inhibitor of bacterial AraC family activators.Journal of biomolecular screening · 2013Article
- Development and application of a cellular, gain-of-signal, bioluminescent reporter screen for inhibitors of type II secretion in Pseudomonas aeruginosa and Burkholderia pseudomallei.Journal of biomolecular screening · 2011Article
- Protein export systems of Mycobacterium tuberculosis: novel targets for drug development?Future microbiology · 2010Review
- Novel whole-cell antibiotic biosensors for compound discovery.Applied and environmental microbiology · 2007Article
- Identification of antibiotic stress-inducible promoters: a systematic approach to novel pathway-specific reporter assays for antibacterial drug discovery.Genome research · 2004Article
- A genomics-based approach to biodefence preparedness.Nature reviews. Genetics · 2004Review
- Stress-based identification and classification of antibacterial agents: second-generation Escherichia coli reporter strains and optimization of detection.Antimicrobial agents and chemotherapy · 2002Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein secretion is an essential process for bacterial growth, yet there are few if any antimicrobial agents which inhibit secretion. An in vivo, high-throughput screen to detect secretion inhibitors was developed based on the translational autoregulation of one of the central protein components, SecA. The assay makes use of a SecA-LacZ fusion reporter construct in Escherichia coli which is induced when secretion is perturbed. Several compounds, including two natural product extracts, which had the ability to induce the reporter fusion were identified and the MICs of these compounds for Staphylococcus aureus strain MN8 were found to be < or =128 microg/ml. Enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation techniques were used to analyze the affects of these compounds on protein secretion. Six representative compounds presented here appear to be bona fide secretion inhibitors but were found to have deleterious effects on membranes. It was concluded that, while the method described here for identifying inhibitors of secretion is valid, screens such as this, which are directed against the membrane-bound portion of a pathway, may preferentially identify compounds which affect membrane integrity.
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Registered trials
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