Antibacterial Effect of Some Eukaryotic Sterol Biosynthesis Inhibitors

Abstract

Background: Isoprenoids and their derivatives are building blocks for the synthesis of biomolecules with important biological functions such as cholesterol in eukaryotes and lipid carrier undecaprenol, which is involved in cell wall biosynthesis in bacteria. With the global threat of multidrug-resistant bacteria, there is a need for finding new metabolic targets for killing bacteria. In the present study, we examined the impact of eukaryotic sterol biosynthesis inhibitors on the growth of four pathogenic bacteria. Materials and Methods: Antibacterial effect of HMG CoA reductase inhibitor (simvastatin), farnesyl pyrophosphate synthase inhibitor (alendronate), squalene epoxidase inhibitor (terbinafine), and lanosterol demethylase inhibitor (ketoconazole) were studied against four pathogenic bacteria: two gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis and two gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa . Broth microdilution method was used for assessing the antibacterial susceptibility of the components using 96 well plats. MIC and MBC were determined visibly. Results: MIC of Ketoconazole for Staphylococcus aureus and Enterococcus faecalis were 0.166 and 1 mg/mL, respectively. Terbinafine had a weak inhibitory effect on Staphylococcus aureus (MIC: 8 mg/mL). Ketoconazole and terbinafine had no inhibitory effect on gram-negative bacteria. MBC of Simvastatin for both Staphylococcus aureus and Enterococcus faecalis was 0.5 mg/mL and of Alendronate for Pseudomonas aeruginosa was 6.6 mg/mL. Conclusion: Our results show that farnesyl pyrophosphate synthase and class II HMG-CoA reductases inhibitors (ketoconazole and simvastatin) have reasonable antibacterial activity against gram-positive bacteria. These two enzymes provide suitable targets for designing new antibiotics based on modifying the chemical structure of currently used drugs to obtain maximum activity.

Harnessing cGAS–STING axis for therapeutic benefits in systemic lupus erythematosus

“…18,19 Despite viral infection, cGAS stimulation can also be triggered by host DNA. 14,20,21 Theoretically, autoimmunity might result from the cGAS abnormally detecting self-DNA, according to the original definition of intracellular DNA sensing. [22][23][24] Numerous varieties of DNA damage, both exogenous and endogenous, are possible sources of these DNAs.…”

“…Despite viral infection, cGAS stimulation can also be triggered by host DNA 14,20,21 . Theoretically, autoimmunity might result from the cGAS abnormally detecting self‐DNA, according to the original definition of intracellular DNA sensing 22–24 .…”