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Repurposing metformin as a dual-function agent to combat E. coli-induced mastitis: Mechanistic insights into biofilm dispersion and AMPK/SIRT1-mediated NF-κB inhibition - PubMed

5 days ago
  • #metformin
  • #mastitis
  • #antimicrobial resistance
  • Metformin repurposed as a dual-function agent against E. coli-induced mastitis.
  • Targets bacterial virulence (biofilm dispersion) and host inflammation (AMPK/SIRT1-mediated NF-κB inhibition).
  • Phylogroup B1 identified as the most prevalent and resistant E. coli lineage (52.5%).
  • Metformin inhibits and disperses biofilms, synergizing with β-lactam antibiotics.
  • Downregulates bacterial genes critical for membrane integrity and metabolism.
  • Attenuates inflammatory response in bovine mammary epithelial cells and animal models.
  • Reduces bacterial colonization and suppresses pro-inflammatory cytokines in vivo.
  • Mechanism involves AMPK/SIRT1 activation leading to NF-κB p65 deacetylation.
  • Epigenetic regulation observed with increased chromatin compaction at inflammatory gene promoters.
  • Provides a non-antibiotic strategy to combat antimicrobial resistance in mastitis.