genetic evidence for inhibition of bacterial division protein ftsz by berberine遗传学证据供小檗碱抑制细菌蛋白质ftsz分工.pdfVIP

Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine 1 2 1 Jaroslaw M. Boberek , Jem Stach , Liam Good * 1 Department of Pathology and Infectious Diseases, The Royal Veterinary College, University of London, London, United Kingdom, 2 School of Biology, University of Newcastle, Newcastle upon Tyne, United Kingdom Abstract Background: Berberine is a plant alkaloid that is widely used as an anti-infective in traditional medicine. Escherichia coli exposed to berberine form filaments, suggesting an antibacterial mechanism that involves inhibition of cell division. Berberine is a DNA ligand and may induce filamentation through induction of the SOS response. Also, there is biochemical evidence for berberine inhibition of the cell division protein FtsZ. Here we aimed to assess possible berberine mechanism(s) of action in growing bacteria using genetics tools. Methodology/Principal Findings: First, we tested whether berberine inhibits bacterial growth through DNA damage and induction of the SOS response. The SOS response induced by berberine was much lower compared to that induced by mitomycin C in an SOS response reporter strain. Also, cell filamentation was observed in an SOS-negative E. coli strain. To test whether berberine inhibits FtsZ, we assessed its effects on formation of the cell division Z-rings, and observed a dramatic reduction in Z-rings in the presence of berberine. We next used two different strategies for RNA silencing of ftsZ and both resulted in sensitisation of bacteria to berberine, visible as a drop in the Minimum Inhibitory Concentration (MIC). Furthermore, Fractional Inhibitory Concentration Indices (FICIs) showed a high level of synergy between ftsZ silencing and berberine treatment (FICI values