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J Vet Sci. 2018 Oct 8. [Epub ahead of print]

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

Shi C1,2, Li M1,2, Muhammad I1,2, Ma X3, Chang Y1,2, Li R1,2, Li C3, He J1,2, Liu F1,2.

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College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin, China.
Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.


Bacterial biofilms have been demonstrated to be closely related to clinical infections and mainly 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 combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and the effect on the related genes (rpoE, luxS, ompR) expressions. The fractional inhibitory concentration index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm adhesion rate and growth curve showed that the multi-resistant Salmonella strain had potential ability to form biofilm relative to CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at 1/2×MIC/FIC concentrations, and the combination showed stronger antibiofilm effect than each of the antimicrobial agent 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 combination repressed mRNA expressions more strongly at 1/4×FIC concentration. The results indicated that the combination of berberine and CIP showed synergistic effect and more effective to inhibit Salmonella biofilm formation via repression of luxS, rpoE and ompR mRNA expressions.


Salmonella; berberine; biofilm formation; drug combination; multi-resistance


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