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Antibacterial and Antibiofilm Activity of Closantel Against Staphylococcus epidermidis
Wu Pingyun1,2, Wu Yuan1, Wu Ruolan1
1Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, China.
Abstract:
Staphylococcus epidermidis is recognized as the major cause of implanted indwelling medical device-related infections. The ability of S. epidermidis to form biofilms largely increases its resistance to conventional antibiotics, which is the major cause of treatment failure. Therefore, there is a pressing need to discover novel antimicrobials against S. epidermidis biofilms. In this study, Closantel (Clos), an antiparasitic drug, was repurposed to be effective against S. epidermidis planktonic cells with the minimal inhibitory concentration values of 0.25-0.5 μg/mL. Clos exhibited potent biofilm inhibition at ≥ 0.5 μg/mL and achieved effective eradication at ≥ 1 μg/mL. Notably, Clos induced lower resistance in S. epidermidis compared to Rifampicin. Mechanism study indicated that Clos exerted the bactericidal activity mainly through inducing bacterial cell membrane depolarization and further disruption. And the antibiofilm activity of Clos could be partially due to the inhibition of initial adhesion and extracellular polysaccharides production. In addition, CCK-8 assay showed that Clos at 16 μg/mL had limited cytotoxicity in A2780, HaCaT and 293 T cells. In conclusion, this study demonstrates that Clos, a molecule targeting bacterial cell membranes, exhibits strong antimicrobial and antibiofilm effects in vitro against S. epidermidis. Although, side effects were reported in mammals, developing Clos derivatives could be still an effective therapeutic strategy to treat S. epidermidis-related infections.
Insights
Closantel (Clos), an antiparasitic drug, shows potent antimicrobial and antibiofilm activity against Staphylococcus epidermidis infections. This repurposed drug effectively inhibits and eradicates biofilms, offering a promising strategy for medical device-related infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Staphylococcus epidermidis is a primary cause of medical device-related infections.
- S. epidermidis biofilms exhibit high resistance to antibiotics, leading to treatment failures.
- Novel antimicrobials targeting S. epidermidis biofilms are urgently needed.
Purpose of the Study:
- To investigate the repurposed antiparasitic drug Closantel (Clos) as a novel antimicrobial agent against S. epidermidis.
- To evaluate Clos's efficacy in inhibiting and eradicating S. epidermidis biofilms.
- To explore the mechanism of action and cytotoxicity of Clos.
Main Methods:
- Minimal inhibitory concentration (MIC) determination for planktonic S. epidermidis.
- Biofilm inhibition and eradication assays at various Clos concentrations.
- Bactericidal activity mechanism study involving cell membrane depolarization.
- Cytotoxicity assessment using CCK-8 assays on mammalian cell lines.
Main Results:
- Clos demonstrated potent activity against planktonic S. epidermidis (MIC: 0.25-0.5 μg/mL).
- Clos effectively inhibited biofilms at ≥0.5 μg/mL and eradicated them at ≥1 μg/mL.
- Clos induced less resistance compared to Rifampicin and acted by disrupting bacterial cell membranes.
- Clos showed limited cytotoxicity in tested mammalian cell lines.
Conclusions:
- Closantel exhibits significant antimicrobial and antibiofilm effects against S. epidermidis in vitro.
- Clos targets bacterial cell membranes, offering a novel mechanism against resistant biofilms.
- Developing Clos derivatives presents a potential therapeutic strategy for S. epidermidis infections despite reported mammalian side effects.
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