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Dimethyl fumarate alleviates Staphylococcus pseudintermedius-induced cell damage by inhibiting pyroptosis and

Zhihao Wang1, Long Guo1, Pengfei Dong1

  • 1College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China.

Experimental Eye Research
|December 16, 2024
PubMed

Insights

Dimethyl fumarate (DMF) shows promise against bacterial keratitis by reducing inflammation and inhibiting Staphylococcus pseudintermedius growth and biofilm formation. This study highlights DMF

Area of Science:

  • Ophthalmology
  • Microbiology
  • Immunology

Background:

  • Antibiotic resistance in bacterial keratitis poses a significant clinical challenge.
  • Dimethyl fumarate (DMF) has known anti-inflammatory effects but its role in bacterial keratitis is unexplored.

Purpose of the Study:

  • To investigate the anti-inflammatory and antibacterial effects of Dimethyl fumarate (DMF) in bacterial keratitis.
  • To evaluate DMF's impact on the pyroptosis pathway and virulence factors of Staphylococcus pseudintermedius.

Main Methods:

  • Established a pyroptosis model using canine corneal epithelial cells (CCECs) infected with Staphylococcus pseudintermedius.
  • Utilized Western blot, ELISA, immunostaining, flow cytometry, and qRT-PCR to analyze cellular pathways and gene expression.
  • Assessed the effect of varying DMF concentrations on bacterial growth, biofilm formation, and clinical isolates.

Main Results:

  • DMF inhibited the NLRP3-GSDMD pathway and pyroptosis while activating the NRF2 pathway, reducing intracellular bacteria and ROS.
  • DMF suppressed the mRNA expression of key Staphylococcus pseudintermedius virulence genes.
  • DMF demonstrated dose-dependent inhibition of bacterial growth and biofilm formation in clinical isolates.

Conclusions:

  • Dimethyl fumarate exhibits significant anti-inflammatory and antibacterial properties against Staphylococcus pseudintermedius.
  • DMF effectively reduces pyroptosis and bacterial proliferation, suggesting its potential as a novel ophthalmic therapeutic agent.
Keywords:
Anti-inflammatoryAntibacterialDimethyl fumaratePyroptosisStaphylococcus pseudintermedius

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