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Inhibitory effects of simeprevir on Staphylococcusepidermidis and itsbiofilm in vitro
Yingjia Li1, Chaoni Cai2,3, Zixin Liu2,4
1Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013. lyj1260731@126.com.
Objectives:
Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro.
Methods:
The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay.
Results:
Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5.
Conclusions:
Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.
Insights
Simeprevir, an antiviral drug, effectively combats Staphylococcus epidermidis infections by inhibiting bacterial growth and biofilm formation. It shows synergistic effects with gentamicin, offering a potential new treatment for drug-resistant strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Staphylococcus epidermidis is a major cause of hospital-acquired infections.
- Increasing antibiotic resistance necessitates novel therapeutic strategies like drug repurposing.
- Simeprevir, an antiviral drug, is explored for its potential against resistant bacteria.
Purpose of the Study:
- To investigate the antimicrobial and antibiofilm effects of simeprevir against Staphylococcus epidermidis.
- To evaluate simeprevir's efficacy as a potential treatment for S. epidermidis infections.
Main Methods:
- Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) assays.
- Crystal violet staining for biofilm inhibition.
- SYTO9/PI fluorescent staining for antimicrobial activity.
- Checkerboard and time-inhibition assays for drug synergy with gentamicin.
Main Results:
- Simeprevir demonstrated significant antimicrobial activity against S. epidermidis strains (MIC: 2-16 μg/mL, MBC: 4-32 μg/mL).
- Simeprevir effectively inhibited and disrupted S. epidermidis biofilms on various surfaces.
- A synergistic antimicrobial effect was observed between simeprevir and gentamicin.
Conclusions:
- Simeprevir possesses notable antimicrobial and anti-biofilm properties against Staphylococcus epidermidis.
- Drug repurposing of simeprevir presents a promising avenue for treating S. epidermidis infections, especially drug-resistant strains.
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