title: Statins and Antimicrobial Effects: Simvastatin as a Potential Drug against Staphylococcus aureus Biofilm.
abstract: Statins are important lipid-lowering agents with other pleiotropic effects. Several studies have explored a possible protective effect of statins to reduce the morbidity and mortality of many infectious diseases. Staphylococcus aureus is one of the main pathogens implicated in nosocomial infections; its ability to form biofilms makes treatment difficult. The present study observed the MIC of atorvastatin, pravastatin and simvastatin against S. aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis. Simvastatin was the only agent with activity against clinical isolates and reference strains of methicilin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Thus, the effects of simvastatin on the growth, viability and biofilm formation of S. aureus were tested. In addition, a possible synergistic effect between simvastatin and vancomycin was evaluated. Simvastatin's MIC was 15.65 µg/mL for S. aureus 29213 and 31.25 µg/mL for the other strains of S. aureus. The effect of simvastatin was bactericidal at 4xMIC and bacteriostatic at the MIC concentration. No synergistic effect was found between simvastatin and vancomycin. However, the results obtained against S. aureus biofilms showed that, in addition to inhibiting adhesion and biofilm formation at concentrations from 1/16xMIC to 4xMIC, simvastatin was also able to act against mature biofilms, reducing cell viability and extra-polysaccharide production. In conclusion, simvastatin showed pronounced antimicrobial activity against S. aureus biofilms, reducing their formation and viability.
authors.affiliation: Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Talita Signoreti
authors.initials: TS
authors.lastname: Graziano
authors.affiliation: Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Cuzzullin
authors.affiliation: Department of General Biology, Area of Physiology and Pathophysiology, State University of Ponta Grossa, Paraná, Brazil.
authors.forename: Gilson Cesar
authors.initials: GC
authors.lastname: Franco
authors.affiliation: Department of Dentistry, Implantology Area, University of Santo Amaro, São Paulo, São Paulo, Brazil.
authors.forename: Humberto Osvaldo
authors.initials: HO
authors.lastname: Schwartz-Filho
authors.affiliation: Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Eduardo Dias
authors.initials: ED
authors.lastname: de Andrade
authors.affiliation: Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Groppo
authors.affiliation: Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, São Paulo, Brazil; Department of Dentistry, Implantology Area, University of Santo Amaro, São Paulo, São Paulo, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Cogo-Müller
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D058492:Drug Repositioning; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D019821:Simvastatin / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D014640:Vancomycin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin