ArticlePLoS biology2023
Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 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
6 citing papers in PubMed, 12 citations in OpenAlex.
- Expression patterns of core metabolic genes and elevated intracellular ROS confer drug tolerance inMicrobiology spectrum · 2026Article
- Stevioside curbs Streptococcus pneumoniae infection via inhibiting capsule biosynthesis.Communications biology · 2026Article
- Alterations in nutrient availability in the lungs duringInfection and immunity · 2025Article
- Metabolic Rewiring of Bacterial Pathogens in Response to Antibiotic Pressure-A Molecular Perspective.International journal of molecular sciences · 2025Review
- Glutathione reductase modulates endogenous oxidative stress and affects growth and virulence in Avibacterium paragallinarum.Veterinary research · 2025Article
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Anaerobic bacteria are responsible for half of all pulmonary infections. One such pathogen is Streptococcus pneumoniae (Spn), a leading cause of community-acquired pneumonia, bacteremia/sepsis, and meningitis. Using a panel of isogenic mutants deficient in lactate, acetyl-CoA, and ethanol fermentation, as well as pharmacological inhibition, we observed that NAD(H) redox balance during fermentation was vital for Spn energy generation, capsule production, and in vivo fitness. Redox balance disruption in fermentation pathway-specific fashion substantially enhanced susceptibility to killing in antimicrobial class-specific manner. Blocking of alcohol dehydrogenase activity with 4-methylpyrazole (fomepizole), an FDA-approved drug used as an antidote for toxic alcohol ingestion, enhanced susceptibility of multidrug-resistant Spn to erythromycin and reduced bacterial burden in the lungs of mice with pneumonia and prevented the development of invasive disease. Our results indicate fermentation enzymes are de novo targets for antibiotic development and a novel strategy to combat multidrug-resistant pathogens.
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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.