title: In vitro characterization and inhibition of the interaction between ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae.
abstract: Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Ye
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: He
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Su-Rong
authors.initials: SR
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Ruo-Lun
authors.initials: RL
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Zhuo-Shan
authors.initials: ZS
authors.lastname: He
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests
chemical_list: C477884:AcrR protein, Klebsiella pneumoniae; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D001599:Berberine; D002939:Ciprofloxacin