Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR

J Vet Sci. 2018 Nov 30;19(6):808-816. doi: 10.4142/jvs.2018.19.6.808.


Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at 1/2 × MIC/FIC concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at 1/4 × FIC concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p < 0.01) at 1/2 × MIC/FIC concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the 1/4 × FIC concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.

Keywords: Salmonella; berberine; biofilm; drug combinations; multidrug resistance.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Berberine / administration & dosage
  • Berberine / pharmacology*
  • Biofilms / drug effects*
  • Carbon-Sulfur Lyases / genetics
  • Carbon-Sulfur Lyases / metabolism*
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Microbial Sensitivity Tests
  • RNA, Messenger / genetics
  • Salmonella / drug effects*
  • Sigma Factor / genetics
  • Sigma Factor / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • RNA, Messenger
  • Sigma Factor
  • Trans-Activators
  • osmolarity response regulator proteins
  • sporulation-specific sigma factors
  • Berberine
  • Ciprofloxacin
  • Carbon-Sulfur Lyases
  • LuxS protein, Bacteria