Effects of simvastatin on the mevalonate pathway and cell wall integrity of Staphylococcus aureus

Abstract Aims To investigate the effects of simvastatin as an antimicrobial, considering its influence on the mevalonate pathway and on the bacterial cell wall of Staphylococcus aureus. Methods and results S. aureus ATCC 29213 and 33591 were exposed to simvastatin in the presence of exogenous mevalonate to determine whether mevalonate could reverse the inhibition. S. aureus was also treated with simvastatin and gene expression analysis assays were performed to evaluate genes associated with the mevalonate pathway (mvaA, mvaS, mvaK1, and mvaK2), peptidoglycan synthesis (uppS, uppP, and murG), and cell wall stress (vraX, sgtB, and tcaA). Transmission electron microscopy was used to identify the presence of morphological changes. The data were compared using two-way ANOVA and Bonferroni post-test, or the Mann-Whitney test. Addition of exogenous mevalonate was able to partially or completely reverse the inhibition caused by simvastatin. A significant increase of the vraX gene and a reduction of the mvaA gene were observed, together with changes in bacterial morphology. Conclusion Simvastatin can exert its antimicrobial effect by means of changes in the cell wall associated with the mevalonate pathway.