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

Abstract

Background

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 (AgNP_bio) 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. AgNP_bio 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-AgNP_bio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNP_bio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNP_bio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA.

Conclusion

Our results indicate that the combination of AgNP_bio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNP_bio are required, with the same antibacterial activity.

Keywords:

• antibacterial
• metallic nanoparticles
• multidrug-resistant bacterial
• statins
• synergism

Acknowledgments

This study was supported by CNPq BIOTEC 402728/2013-0 and CAPES, which made this study possible. Support from INOMAT (MCTI/CNPq), NanoBioss (MCTI), and the Brazilian Network of Nanotoxicology (MCTI/CNPq) is also acknowledged. The authors would also like to thank the Laboratory for Electron Microscopy and Microanalysis – LMEM/Universidade Estadual de Londrina and Central de Microscopia – COMCAP/Universidade Estadual de Maringá for help with the electron microscopy experiments. We thank Dr. Elsa Masae and Dr. Agnes Marie Sá Figueiredo who donated the MRSA N315 and MRSA BEC9393 strains. Dr. A. Leyva helped with English editing of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.