ArticleACS medicinal chemistry letters2016
Novel Inhibitors of Toxin HipA Reduce Multidrug Tolerant Persisters.
Article in ACS medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Protein-Protein Interactions as Promising Molecular Targets for Novel Antimicrobials Aimed at Gram-Negative Bacteria.International journal of molecular sciences · 2025Review
- Persistence and Culturability ofAntibiotics (Basel, Switzerland) · 2024Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- Stapled Phd Peptides Inhibit Doc Toxin Induced Growth Arrest inACS chemical biology · 2023Article
- Review
- A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.International journal of molecular sciences · 2022Review
- Modulators of protein-protein interactions as antimicrobial agents.RSC chemical biology · 2021Review
- Article
- Review
- The Development of Target-Specific Pose Filter Ensembles To Boost Ligand Enrichment for Structure-Based Virtual Screening.Journal of chemical information and modeling · 2017Article
- Gene Expression Profiling of Transcription Factors ofFrontiers in microbiology · 2017Article
- Transcriptional Profiling of Type II Toxin-Antitoxin Genes ofFrontiers in microbiology · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persisters are a small fraction of drug-tolerant bacteria without any genotype variations. Their existence in many life-threatening infectious diseases presents a major challenge to antibiotic therapy. Persistence is highly related to toxin-antitoxin modules. HipA (high persistence A) was the first toxin found to contribute to Escherichia coli persistence. In this study, we used structure-based virtual screening for HipA inhibitors discovery and identified several novel inhibitors of HipA that remarkably reduced E. coli persistence. The most potent one decreased the persister fraction by more than five-fold with an in vitro K D of 270 ± 90 nM and an ex vivo EC50 of 46 ± 2 and 28 ± 1 μM for ampicillin and kanamycin screening, respectively. These findings demonstrated that inhibition of toxin can reduce bacterial persistence independent of the antibiotics used and provided a framework for persistence treatment by interfering with the toxin-antitoxin modules.
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