ArticleACS infectious diseases2018
Inhibitors of LexA Autoproteolysis and the Bacterial SOS Response Discovered by an Academic-Industry Partnership.
Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 63 citations in OpenAlex.
- Antiphage defence systems Druantia III and Zorya II synergise via shared DNA intermediates in a phage-specific manner.bioRxiv : the preprint server for biology · 2026Article
- Benzoxaborole-Based Inhibitors Block LexA Autocleavage and Suppress SOS-Dependent Adaptive Phenotypes inAntibiotics (Basel, Switzerland) · 2026Article
- Regulation of drug resistance to enrofloxacin inFrontiers in microbiology · 2026Article
- Integrated omics reveal a unique antibacterial mechanism of action for the small molecule HSI#6.Current research in microbial sciences · 2026Article
- Identification and Characterization of a Small-Molecule Inhibitor of theACS infectious diseases · 2025Article
- Snapshots ofiScience · 2025Article
- Insights into antibiotic resistance promoted by quinolone exposure.Antimicrobial agents and chemotherapy · 2025Article
- Cooperative mechanisms of LexA and HtpG in the regulation of virulence gene expression inCurrent research in microbial sciences · 2025Article
- The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation.Nature structural & molecular biology · 2024Article
- Review
- A small molecule that inhibits the evolution of antibiotic resistance.NAR molecular medicine · 2024Article
- Structural basis for regulation of SOS response in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Integration of molecular modelling andFrontiers in cellular and infection microbiology · 2023Article
- Engineered RecA Constructs Reveal the Minimal SOS Activation Complex.Biochemistry · 2022Article
- The DdrR Coregulator of the Acinetobacter baumannii Mutagenic DNA Damage Response Potentiates UmuDAb Repression of Error-Prone Polymerases.Journal of bacteriology · 2022Article
- Filamentous morphology of bacterial pathogens: regulatory factors and control strategies.Applied microbiology and biotechnology · 2022Review
- Bacterial Stress Responses as Potential Targets in Overcoming Antibiotic Resistance.Microorganisms · 2022Review
- Stress-Induced Mutagenesis, Gambler Cells, and Stealth Targeting Antibiotic-Induced Evolution.mBio · 2022Review
- Exploration of inhibitors of the bacterial LexA repressor-protease.Bioorganic & medicinal chemistry letters · 2022Article
- Activation of class 1 integron integrase is promoted in the intestinal environment.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The RecA/LexA axis of the bacterial DNA damage (SOS) response is a promising, yet nontraditional, drug target. The SOS response is initiated upon genotoxic stress, when RecA, a DNA damage sensor, induces LexA, the SOS repressor, to undergo autoproteolysis, thereby derepressing downstream genes that can mediate DNA repair and accelerate mutagenesis. As genetic inhibition of the SOS response sensitizes bacteria to DNA damaging antibiotics and decreases acquired resistance, inhibitors of the RecA/LexA axis could potentiate our current antibiotic arsenal. Compounds targeting RecA, which has many mammalian homologues, have been reported; however, small-molecules targeting LexA autoproteolysis, a reaction unique to the prokaryotic SOS response, have remained elusive. Here, we describe the logistics and accomplishments of an academic-industry partnership formed to pursue inhibitors against the RecA/LexA axis. A novel fluorescence polarization assay reporting on RecA-induced self-cleavage of LexA enabled the screening of 1.8 million compounds. Follow-up studies on select leads show distinct activity patterns in orthogonal assays, including several with activity in cell-based assays reporting on SOS activation. Mechanistic assays demonstrate that we have identified first-in-class small molecules that specifically target the LexA autoproteolysis step in SOS activation. Our efforts establish a realistic example for navigating academic-industry partnerships in pursuit of anti-infective drugs and offer starting points for dedicated lead optimization of SOS inhibitors that could act as adjuvants for current antibiotics.
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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.