A potential plasmid-curing agent, 8-epidiosbulbin E acetate, from Dioscorea bulbifera L. against multidrug-resistant bacteria.
Bioassay-guided fractionation of an aqueous methanolic extract of Dioscorea bulbifera L. bulbs was performed using organic solvents. A novel plasmid-curing compound was identified as 8-epidiosbulbin E acetate (EEA) (norditerpene) on the basis of modern spectroscopic analysis and X-ray crystallography. EEA exhibited broad-spectrum plasmid-curing activity against multidrug-resistant (MDR) bacteria, including vancomycin-resistant enterococci. EEA cured antibiotic resistance plasmids (R-plasmids) from clinical isolates of Enterococcus faecalis, Escherichia coli, Shigella sonnei and Pseudomonas aeruginosa with 12-48% curing efficiency. The reference plasmids of Bacillus subtilis (pUB110), E. coli (RP4), P. aeruginosa (RIP64) and Salmonella typhi (R136) were cured with efficiency ranging from 16% to 64%. EEA-mediated R-plasmid curing decreased the minimal inhibitory concentration of antibiotics against MDR bacteria, thus making antibiotic treatment more effective. The antibiotic resistance pattern revealed that the compound was effective in the reversal of bacterial resistance to various antibiotics. In addition, the compound did not show any cytotoxicity against a broad range of human cancer cell lines, namely MCF-7 (breast cancer), SiHa (cervical cancer) and A431 (epidermal carcinoma), and hence has the potential to be used as a lead compound for drug discovery programmes.
Shriram
Varsha
V
Department of Botany, University of Pune, Pune 411 007, India.
Jahagirdar
Sheetal
S
Latha
C
C
Kumar
Vinay
V
Puranik
Vedavati
V
Rojatkar
Supada
S
Dhakephalkar
Prashant K
PK
Shitole
M G
MG
D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D004269:DNA, Bacterial / Q000187:drug effects / Q000235:genetics; D027742:Dioscorea / Q000737:chemistry*; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010957:Plasmids / Q000187:drug effects*; D014961:X-Ray Diffraction
C534602:8-epidiosbulbin E acetate; D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D004269:DNA, Bacterial; D004224:Diterpenes; D010936:Plant Extracts