New Approach For Simvastatin As An Antibacterial: Synergistic Effect With Bio-Synthesized Silver Nanoparticles Against Multidrug-Resistant Bacteria

EP Figueiredo,1 JM Ribeiro,1 EK Nishio,1 S Scandorieiro,1 AF Costa,2 VF Cardozo,1 AG Oliveira,1 N Durán,2–4 LA Panagio,1 RKT Kobayashi,1 G Nakazato1 1Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina, Paraná, Brazil; 2NanoBioss, Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil; 3Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil; 4LNNano (National Laboratory of Nanotecnology), CNPEM, Campinas, São Paulo, BrazilCorrespondence: G NakazatoDepartment of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Campus Universitário, CEP, Londrina 86055-990, Paraná, BrazilTel +55 43 3371 4396Fax +55 43 3371 4788Email gersonakazato@yahoo.com.brBackground: Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections.Methods: Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by Fusarium oxysporum (AgNPbio) in combination with simvastatin against reference and multidrug-resistant bacterial strains.Results: Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL−1 against MRSA. AgNPbio with a size of 77.68± 33.95 nm and zeta potential −34.6 ± 12.7 mV showed an MIC of 0.212 mg mL−1 against S. aureus including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNPbio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNPbio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNPbio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA.Conclusion: Our results indicate that the combination of AgNPbio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNPbio are required, with the same antibacterial activity.Keywords: antibacterial, metallic nanoparticles, multidrug-resistant bacterial, statins, synergism