Modulation of Staphylococcus aureus Biofilm Formation through Subinhibitory Concentrations of Biogenic Silver Nanoparticles and Simvastatin

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant and biofilm-forming pathogenic bacteria with severe morbidity and mortality. MRSA showed resistance against currently available antibiotics. Thus, there is an urgent need to develop novel effective treatments with minimal side effects to eliminate MRSA.AimIn this study, we aimed to mycosynthesize silver nanoparticles (AgNPs) using the endophytic fungus Aspergillus parasiticus isolated from leaves of Reseda Arabica and to examine their antibacterial activity against MRSA.ResultsScreening of fungal secondary metabolites using gas chromatography–mass spectroscopy (GC–MS) analysis revealed the presence of high content of bioactive compounds with antibacterial activities. AP-AgNPs were mycosynthesized for the first time using ethyl acetate extract of A. parasiticus and characterized by imaging (transmission electron microscopy (TEM), UV–Vis spectroscopy, zeta potential, X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR)). The agar well diffusion method revealed the antibacterial activity of AP-AgNPs against MRSA with 25 μg/mL of minimum inhibitory concentration (MIC). AP-AgNPs were shown to exert antibacterial action via a bactericidal mechanism based on flow cytometry, scanning electron microscopy, and transmission electron microscopy assessment. Our data demonstrated the effective interaction of AP-AgNPs with the bacterial cell membrane, which resulted in cell membrane damage and disruption of cell surface structure. Furthermore, AP-AgNPs successfully prevented the development of MRSA biofilms by disturbing cell adhesion and destructing mature biofilm reaching over 80% clearance rate. Interestingly, topical application of AP-AgNPs to superficial skin infection induced by MRSA in mice effectively promoted wound healing and suppressed bacterial burden.ConclusionOur results provide a novel green nanoparticle drug design with effective therapeutic potential against MRSA-induced skin infection.

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Biosynthesis and Characterization of Silver Nanoparticles and Simvastatin Association in Titanium Biofilms

Roque,

Furian,

Takemoto

et al. 2024

Pharmaceuticals

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Introduction: Simvastatin is an antilipidemic drug that has already demonstrated antibacterial activities on oral and non-oral microorganisms. Silver nanoparticles also exhibit antimicrobial properties, particularly for coating implant surfaces. In this study, we evaluated the effects of combining simvastatin with silver nanoparticles on the formation and viability of biofilms consolidated on titanium discs. Methods: Silver nanoparticles were first biosynthesized using the fungus Fusarium oxysporum and then characterized using Dynamic Light Scattering, X-ray Diffraction, Transmission Electron Microscopy, and energy dispersive spectroscopy. Species of Streptococcus oralis, Streptococcus mutans, Porphyromonas gingivalis, Methicillin-sensitive Staphylococcus aureus, and Methicillin-resistant Staphylococcus aureus were used and tested using Minimum Inhibitory Concentration assays with concentrations of silver nanoparticles and simvastatin alone and in combination. Biofilm inhibition and viability tests were performed on titanium surfaces. Toxicity tests were also performed on Galleria mellonella moth larvae. Results: The silver nanoparticles had a spherical shape without the formation of aggregates as confirmed by Transmission Electron Microscopy. Dynamic Light Scattering revealed nanoparticles with an average diameter of 53.8 nm (±1.23 nm), a polydispersity index of 0.23 and a zeta potential of −25 mV (±2.19 mV). The silver nanoparticles inhibited the growth of the strains tested in the range of 0.001592 and 63.75, while simvastatin alone inhibited the growth of the same strains in the range of 3.125–62.5 µg/mL. The antibacterial activity test of the combination of the two substances showed a reduction in the Minimum Inhibitory Concentration of about two to eight times, showing synergistic effects on Staphylococcus aureus and additive effects on Streptococcus oralis and Porphyromonas gingivalis. As for biofilm, sub-inhibitory concentrations of the combination of substances showed better antibacterial activity in inhibiting the formation of Streptococcus oralis biofilm, and this combination also proved effective in eradicating already established biofilms compared to the substances alone. The combination of silver nanoparticles and simvastatin showed low toxicity to Galleria mellonella moth larvae. Conclusions: The results presented indicate that the combination of the two substances could be an alternative for the prevention and reduction of biofilms on implants. These findings open up new possibilities in the search for alternatives for the treatment of peri-implant infections, as well as the possibility of using lower doses compared to single drugs, achieving the same results and reducing potential toxic effects.

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Modulation of Staphylococcus aureus Biofilm Formation through Subinhibitory Concentrations of Biogenic Silver Nanoparticles and Simvastatin

Cited by 4 publications

References 78 publications

Repurposing simvastatin for treatment of Klebsiella pneumoniae infections: in vitro and in vivo study

Repurposing simvastatin for treatment of Klebsiella pneumoniae infections: in vitro and in vivo study

Mycosynthesis of silver nanoparticles from endophytic Aspergillus parasiticus and their antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo

Biosynthesis and Characterization of Silver Nanoparticles and Simvastatin Association in Titanium Biofilms

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