Evaluation of Simvastatin effects on gene expression of cell wall precursors in Staphylococcus aureus

Resumo

Staphylococcus aureus infections are difficult to treat due to their ability to form biofilm and their resistance to antibiotics. Studies have shown that simvastatin has an antimicrobial effect against S. aureus, possibly due to the inhibition of the HMG-CoA reductase enzyme at early steps of the mevalonate pathway. This pathway generates important intermediates for the synthesis of peptideoglycans from prokaryotes cell wall. Therefore, the antimicrobial mechanism of action of statins is not understood. Thus, the present study investigated the antimicrobial activity and action of simvastatin on the mevalonate pathway and on cell wall precursors expression of S. aureus. Minimum Inhibitory Concentration (MIC) and time-kill assays with addition of mevalonate were determined for S. aureus ATCC 29213. qRT-PCR were carried out to evaluate the gene expression of uppP, uppS, murG and mraY under simvastatin exposure. MIC for simvastatin was from 31.25 to 15.62 ?g/mL. Mevalonate addition did not altered the bacteriostatic effect of simvastatin (p>0.05, Two-way ANOVA). Gene expression of cell wall precurssors were not altered by 1/4 MIC and 1/8 MIC simvastatin (p>0.05, ANOVA). Therefore, qRT-PCR assays will be repeated to confirm those results. In conclusion, simvastatin may not inhibit mevalonate pathway and cell wall precursors formation. However, more studies need to be carried out to confirm these findings.