Nonselective Mevalonate Kinase Inhibitor as a Novel Class of Antibacterial Agents

摘要

Introduction.There are a few evidences about targeting isoprenoids biosynthesis pathway in bacteria for finding new antibiotics. This study was conducted to assess antibacterial effects of vanadyl sulfate (VS), one of the mevalonate kinase inhibitors to find a new target for killing bacteria.Materials and Methods. Antibacterial effect of VS alone and in combination with glycine or EDTA was assessed onEscherichia coliandPseudomonas aeruginosaas Gram-negative andStaphylococcus aureusandEnterococcus faecalisas Gram-positive bacteria using serial dilution method and minimum inhibitory concentrations (MICs) identified.Result.MICs forS. aureusandE. coliwere 4 and 8 mg/mL, respectively. VS could not affect the growth of two other bacteria. However, VS in combination with glycine not only inhibited the growth ofE. faecalisandP. aeruginosa, but also reduced MICs for VS-sensitive bacteria (S. aureusandE. coli). EDTA could reduce MIC forE. coliandP. aeruginosa.Conclusion.VS could inhibit the growth ofS. aurousandE. coli, and adding glycine or EDTA improved VS antibacterial activity presumably via instability of the cell wall and enhanced transport of VS through bacterial cell wall. Inhibition of the isoprenoid pathway might provide new tools to overcome bacterial resistance.