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

Figures & data

Figure 1 Characterization by transmission electron microscopy (TEM) of AgNP_bio synthesized by Fusarium oxysporum (300,000×).

Figure 2 UV-Vis spectrophotometry of nanoparticles synthetized by Fusarium oxysporum.

Table 1 Results Of Antimicrobial Disk Susceptibility And Minimal Inhibitory Concentration (MIC), Checkerboard, And Fractional Inhibitory Concentration (FICI) For Bacterial Strains

Bacterial strain	Inhibition Zone Size (mm)		Minimal Inhibitory Concentration (MIC)		MIC Of Simvastatin And AgNPbio Combined (mg mL^−1; mg mL^−1)
Sim	AgNPbio	Sim	AgNPbio	Comb	FICI
MSSA ATCC 25923	0	7.33	0.062	0.212	0.015;0.052	0.5(S)
MSSA ATCC 29213	0	7.75	0.062	0.212	0.031;0.052	0.75(A)
MRSA N315	0	7.33	0.062	0.212	0.015;0.052	0.5(S)
MRSA BEC9393	0	8	0.250	0.212	0.031;0.106	0.62(A)
Escherichia coli ESBL 176	0	9.33	>0.250	0.106	0.015;0.052	*
E. coli ATCC 25922	0	8.33	>0.250	0.106	0.062;0.106	*

Notes: MIC: minimal inhibitory concentration; FICI: fractional inhibitory concentration index was calculated as previously described³⁶ and we interpreted it as follows: FICI ≤0.5, synergistic interaction effect; >0.5–1.0, additive interaction effect; >1 and <4, indifferent; ≥4, antagonistic interaction effect. SIM: simvastatin; AgNP_bio: silver nanoparticles obtained by Fusarium oxysporum, Comb: combination of simvastatin and AgNP_bio. Methicillin-resistant Staphylococcus aureus (MRSA); Methicillin-sensitive Staphylococcus aureus (MSSA); American Types Culture Collection (ATCC); Extended-Spectrum Beta-lactamase (ESBL). FICI: (S): synergistic interaction effect; (A): additive interaction effect; *FICI was not calculated.

Figure 3 Time-kill curves for methicillin-resistant Staphylococcus aureus N315. AgNP_bio treatment at a concentration of 212.33 mg mL⁻¹; treatment with 0.062 mg mL⁻¹ simvastatin; AgNP_bio and simvastatin in combination, at concentrations of 53.08 mg mL⁻¹ and 0.015 mg mL⁻¹ respectively. (A) ^aComparison of simvastatin with the combination; ^bcomparison of AgNP_bio with the combination; ^ccomparison of simvastatin with AgNP_bio; ^dtreatments compared to control.

Figure 4 Time-kill curves for extended-spectrum beta lactamases-producing Escherichia coli 176. AgNP_bio treatment at a concentration of 212.33 mg mL⁻¹; treatment with 0.250 mg mL⁻¹ simvastatin; AgNP_bio and simvastatin in combination, at concentrations of 106.16 mg mL⁻¹ and 0.015 mg mL⁻¹, respectively. ^aComparison of simvastatin with the combination; ^bcomparison of AgNP_bio with the combination; ^ccomparison of simvastatin with AgNP_bio; ^dtreatments compared to control.

Figure 5 Scanning electron microscopy (SEM) images of methicillin-resistant Staphylococcus aureus (MRSA) N315 after 3 hrs of incubation. (A) Negative control (not treated) (25,000×). (B) Positive control (50,000×). (C) Treatment with 0.050 mg mL⁻¹ simvastatin (25,000×). (D) Treatment with 0.050 mg mL⁻¹ of simvastatin (50,000×). (E) Treatment with 212.33 mg mL⁻¹ of AgNP_bio (25,000×). (F) Treatment with 212.33 mg mL⁻¹ of AgNP_bio (50,000×). (G) Treatment with 0.012 mg mL⁻¹ of simvastatin and 106.16 mg mL⁻¹ of AgNP_bio in combination (25,000×). (H) Treatment with 0.012 mg mL⁻¹ of simvastatin and 106.16 mg.mL⁻¹ of AgNP_bio in combination (50,000×).

CLSI. M100-S23 Performance Standards for Antimicrobial Susceptibility Testing; Vol 23; 2013.

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