Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria using gel diffusion assay. Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

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 on Escherichia coli and Pseudomonas aeruginosa as Gram-negative and Staphylococcus aureus and Enterococcus faecalis as Gram-positive bacteria using serial dilution method and minimum inhibitory concentrations (MICs) identified. Result. MICs for S. aureus and E. coli were 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 of E. faecalis and P. aeruginosa, but also reduced MICs for VS-sensitive bacteria (S. aureus and E. coli). EDTA could reduce MIC for E. coli and P. aeruginosa. Conclusion. VS could inhibit the growth of S. aurous and E. 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.