ArticleJournal of bacteriology2015
Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by phenotypic screening.
Article in Journal of bacteriology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
- Mechanistic basis of LolDF-mediated lipoprotein transport in Acinetobacter.Nature communications · 2026Article
- Conformational hijacking of lipoprotein transporter LolDF enables precision antimicrobial activity against Acinetobacter baumannii.Nature communications · 2026Article
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Molecular mechanism of action of small molecule SMT-738 on bacterial lipoprotein transporter LolCDE.Nature communications · 2026Article
- Liganded LolCDE structures reveal a common substrate-LolE interaction guiding bacterial lipoprotein transport.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- High-throughput LacZ/CPRG assay for identifying Gram-negative envelope-targeting antibiotics.Frontiers in microbiology · 2026Article
- Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria.Frontiers in microbiology · 2026Review
- How to spare gut microbiota from antibiotic effects? PK-PD based innovative strategies, target specificity, and molecule-to-medicinal properties.RSC medicinal chemistry · 2025Review
- Advances in Small Molecule Inhibitors Targeting the Bacterial Lipoprotein Transport System (Lol) in Gram-Negative Bacteria.Chemistry, an Asian journal · 2025Review
- Global health perspectives on antibacterial drug discovery and the preclinical pipeline.Nature reviews. Microbiology · 2025Review
- Repurposing a drug to punish carbapenem-resistantProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Outer membrane lipoproteins: late to the party, but the center of attention.Journal of bacteriology · 2025Review
- A screen for cell envelope stress uncovers an inhibitor of prolipoprotein diacylglyceryl transferase, Lgt, iniScience · 2024Article
- Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.Pathogens (Basel, Switzerland) · 2024Review
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Dissection of an ABC transporter LolCDE function analyzed by photo-crosslinking.Journal of biochemistry · 2024Article
- Article
- A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli.Cell reports methods · 2024Article
- SMT-738: a novel small-molecule inhibitor of bacterial lipoprotein transport targeting Enterobacteriaceae.Antimicrobial agents and chemotherapy · 2024Article
- Lipoprotein transport system Lol may be a selective target for Gram-negative bacteria.Frontiers in cellular and infection microbiology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Gram-negative bacteria, lipoproteins are transported to the outer membrane by the Lol system. In this process, lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to LolA, a diffusible periplasmic molecular chaperone. Lipoproteins are then transferred to the outer membrane receptor protein, LolB, for insertion in the outer membrane. Here we describe the discovery and characterization of novel pyridineimidazole compounds that inhibit this process. Escherichia coli mutants resistant to the pyridineimidazoles show no cross-resistance to other classes of antibiotics and map to either the LolC or LolE protein of the LolCDE transporter complex. The pyridineimidazoles were shown to inhibit the LolA-dependent release of the lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial cytological profiling are consistent with LolCDE-mediated disruption of lipoprotein targeting to the outer membrane as the mode of action of these pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of the LolCDE complex, a target which has never been exploited for therapeutic intervention. These compounds open the door to further interrogation of the outer membrane lipoprotein transport pathway as a target for antimicrobial therapy.
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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.