Synergistic effect of [10]-gingerol and aminoglycosides against vancomycin-resistant enterococci (VRE).
An extract from ginger (root of Zingiber officinale) reduced the minimum inhibitory concentrations (MICs) of aminoglycosides in vancomycin-resistant enterococci (VRE). The effective compound was isolated and identified as [10]-gingerol. In the presence of [10]-gingerol at 1/10 concentration of its own MIC, the MIC of arbekacin was lowered by 1/32 to 1/16. [10]-Gingerol also reduced the MICs of other aminoglycosides, and of bacitracin and polymixin B, but not of other antimicrobial agents tested. Because [10]-gingerol reduced the MICs of several aminoglycosides both in strains possessing or lacking aminoglycoside-modification enzymes, it seems that the effect of [10]-gingerol is not related to these enzymes, which mainly confer bacterial resistance against aminoglycosides. It seemed that a detergent-like effect of [10]-gingerol potentiated the antimicrobial activity of the aminoglycosides. In fact, some detergents such as sodium dodecyl sulfate (SDS) and Triton X-100 reduced the MICs of aminoglycosides, bacitracin and polymixin B in VRE. Since the intrinsic resistance to aminoglycosides in enterococci is due to low level of entry of the drugs into the cells, increase in the membrane permeability caused by [10]-gingerol will enhance the influx of aminoglycosides into enterococcal cells.
Nagoshi
Chihiro
C
Department of Molecular Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima, Japan.
Shiota
Sumiko
S
Kuroda
Teruo
T
Hatano
Tsutomu
T
Yoshida
Takashi
T
Kariyama
Reiko
R
Tsuchiya
Tomofusa
T
D000123:Acetyltransferases / Q000235:genetics; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002396:Catechols; D002452:Cell Count; D015169:Colony Count, Microbial; D003902:Detergents / Q000494:pharmacology; D003982:Dibekacin / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012967:Sodium Dodecyl Sulfate; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents; D020713:Vancomycin Resistance
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002396:Catechols; D003902:Detergents; D005233:Fatty Alcohols; D009153:Mutagens; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D003982:Dibekacin; C007845:gingerol; C108453:6'-aminoglycoside acetyltransferase-2''-aminoglycoside phosphotransferase; D000123:Acetyltransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C031986:arbekacin