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Carmofur Exhibits Antimicrobial Activity Against Streptococcus pneumoniae

Wenting Lyu1,2,3, Yuqing Zhang1,2,3, Zhen Zhang3

  • 1College of Pharmacy, Heze University, Heze 274000, China.

Antibiotics (Basel, Switzerland)
|March 28, 2025
PubMed

Insights

The anticancer drug carmofur shows potent antibacterial and anti-biofilm activity against multidrug-resistant Streptococcus pneumoniae. This repurposed drug effectively reduces bacterial load and inflammation in vivo, offering a promising new treatment strategy.

Area of Science:

  • Microbiology
  • Pharmacology
  • Drug Discovery

Background:

  • Streptococcus pneumoniae is a significant pathogen with increasing antimicrobial resistance.
  • Developing new antibiotics is challenging, making drug repurposing a viable strategy.
  • Anticancer drugs are being explored for novel antimicrobial applications.

Purpose of the Study:

  • To evaluate the antibacterial and anti-biofilm potential of carmofur against multidrug-resistant S. pneumoniae.
  • To investigate the mechanism of action of carmofur.
  • To assess the in vivo therapeutic efficacy of carmofur.

Main Methods:

  • Antimicrobial susceptibility testing (MICs) and biofilm inhibition assays.
  • Bacterial membrane permeability and intracellular ATP level assessments.
  • Molecular docking, dynamics simulations, and gene expression analysis (thyA).
  • In vivo mouse infection model to evaluate bacterial load, cytokine levels, and survival rates.

Main Results:

  • Carmofur demonstrated potent activity against multidrug-resistant S. pneumoniae (MICs 0.25–1 µg/mL).
  • Carmofur inhibited biofilm formation and eradicated existing biofilms.
  • Mechanism involves disruption of bacterial membrane integrity and inhibition of thymidylate synthase.
  • In vivo studies showed reduced bacterial load, decreased inflammatory cytokines (TNF-α, IL-6), and improved survival (60%).

Conclusions:

  • Carmofur exhibits significant antibacterial and anti-biofilm properties against drug-resistant S. pneumoniae.
  • The drug acts by disrupting membrane permeability and inhibiting thymidylate synthase.
  • Carmofur shows promising therapeutic potential for treating resistant S. pneumoniae infections in vivo.
Keywords:
S. pneumoniaeantibacterialcarmofurmouse pneumoniamultidrug resistant

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