ArticleVirulence2015
Screen of FDA-approved drug library identifies maprotiline, an antibiofilm and antivirulence compound with QseC sensor-kinase dependent activity in Francisella novicida.
Article in Virulence, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 34 citations in OpenAlex.
- Characterization of carABpyrB operon and role of pyrE in Francisella novicida biofilm.MicrobiologyOpen · 2026Article
- Two-component systems as potential therapeutic targets inAnnals of medicine · 2025Review
- Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.Pathogens (Basel, Switzerland) · 2024Review
- Interactions of antidepressants with concomitant medications-safety of complex therapies in multimorbidities.Pharmacological reports : PR · 2024Review
- Galleria mellonella-intracellular bacteria pathogen infection models: the ins and outs.FEMS microbiology reviews · 2023Review
- Efficient Inhibition of Bacterial Biofilm Through Interference of Protein-Protein Interaction of Master Regulator Proteins: a Proof of Concept Study with SinR- SinI Complex of Bacillus subtilis.Applied biochemistry and biotechnology · 2023Article
- Using next generation antimicrobials to target the mechanisms of infection.npj antimicrobials and resistance · 2023Review
- Article
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- Genetic Determinants of Antibiotic Resistance inFrontiers in microbiology · 2021Review
- Unravelling the antimicrobial action of antidepressants on gut commensal microbes.Scientific reports · 2020Article
- The Sensor Kinase QseC Regulates the Unlinked PmrA Response Regulator and Downstream Gene Expression inJournal of bacteriology · 2020Article
- Two-Component Systems inFrontiers in cellular and infection microbiology · 2019Review
- Review
- Options and Limitations in Clinical Investigation of Bacterial Biofilms.Clinical microbiology reviews · 2018Review
- Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics.Current drug targets · 2018Review
- Repurposing Toremifene for Treatment of Oral Bacterial Infections.Antimicrobial agents and chemotherapy · 2017Article
- The orange spotted cockroach (Proceedings of the West Virginia Academy of Science · 2017Article
- QseBC, a two-component bacterial adrenergic receptor and global regulator of virulence in Enterobacteriaceae and Pasteurellaceae.Molecular oral microbiology · 2016Review
- Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing.Virulence · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of new therapeutics against Select Agents such as Francisella is critical preparation in the event of bioterrorism. Testing FDA-approved drugs for this purpose may yield new activities unrelated to their intended purpose and may hasten the discovery of new therapeutics. A library of 420 FDA-approved drugs was screened for antibiofilm activity against a model organism for human tularemia, Francisella (F.) novicida, excluding drugs that significantly inhibited growth. The initial screen was based on the 2-component system (TCS) dependent biofilm effect, thus, the QseC dependence of maprotiline anti-biofilm action was demonstrated. By comparing their FDA-approved uses, chemical structures, and other properties of active drugs, toremifene and polycyclic antidepressants maprotiline and chlorpromazine were identified as being highly active against F. novicida biofilm formation. Further down-selection excluded toremifene for its membrane active activity and chlorpromazine for its high antimicrobial activity. The mode of action of maprotiline against F. novicida was sought. It was demonstrated that maprotiline was able to significantly down-regulate the expression of the virulence factor IglC, encoded on the Francisella Pathogenicity Island (FPI), suggesting that maprotiline is exerting an effect on bacterial virulence. Further studies showed that maprotiline significantly rescued F. novicida infected wax worm larvae. In vivo studies demonstrated that maprotiline treatment could prolong time to disease onset and survival in F. novicida infected mice. These results suggest that an FDA-approved drug such as maprotiline has the potential to combat Francisella infection as an antivirulence agent, and may have utility in combination with antibiotics.
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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.