ArticlemBio2014
QseC inhibitors as an antivirulence approach for Gram-negative pathogens.
Article in mBio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 136 citations in OpenAlex.
- The small molecule regacin binds a conserved pocket in RegA to inhibit the expression of bacterial virulence factors.bioRxiv : the preprint server for biology · 2026Article
- The McbR transcription factor links the intracellular folate pool to virulence in enterohemorrhagicmBio · 2026Article
- The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.Pharmaceutical research · 2025Review
- AACS synthetic biology · 2025Article
- Antibacterial effects of cinnamaldehyde and hesperitin on resistant Glaesserella parasuis by suppressing QseBC two-component system.BMC veterinary research · 2025Article
- "Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration".European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025Article
- Combined transcriptome and metabolome analysis reveals the regulatory network of histidine kinase QseC in the two-component system ofFrontiers in microbiology · 2025Article
- Key roles of two-component systems in intestinal signal sensing and virulence regulation in enterohemorrhagic Escherichia coli.FEMS microbiology reviews · 2024Review
- Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.Pathogens (Basel, Switzerland) · 2024Review
- Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle against Multidrug-Resistant (MDR) Bacteria.Molecules (Basel, Switzerland) · 2024Review
- Quorum sensing-related activities of beneficial and pathogenic bacteria have important implications for plant and human health.FEMS microbiology ecology · 2024Review
- Glucuronic acid confers colonization advantage to enteric pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection.Nature communications · 2024Article
- A bacterial sensor taxonomy across earth ecosystems for machine learning applications.mSystems · 2024Article
- Cross-talk between QseBC and PmrAB two-component systems is crucial for regulation of motility and colistin resistance in Enteropathogenic Escherichia coli.PLoS pathogens · 2023Article
- Light-Based Anti-Biofilm and Antibacterial Strategies.Pharmaceutics · 2023Review
- Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps.Antibiotics (Basel, Switzerland) · 2023Review
- Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Using next generation antimicrobials to target the mechanisms of infection.npj antimicrobials and resistance · 2023Review
- The human microbiome in disease and pathology.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
unlabelledInvasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections. IMPORTANCE: There is an imminent need for development of novel treatments for infectious diseases, given that one of the biggest challenges to medicine in the foreseeable future is the emergence of microbial antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens that promotes their virulence expression. The LED209 QseC inhibitor has a unique mode of action by acting as a prodrug scaffold to deliver a warhead that allosterically modifies QseC, impeding virulence in several Gram-negative pathogens.
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What OpenQuestion holds
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.