Study on antibacterial effect of halicin (SU3327) against Enterococcus faecalis and Enterococcus faecium

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Enterococci are significant causes of hospital-acquired infections.
• Antibiotic resistance in Enterococci necessitates novel therapeutic strategies.
• Drug repurposing offers a promising avenue for developing new antibacterial agents.

Purpose of the Study:

• To evaluate the antimicrobial activity of halicin against Enterococcus species.
• To investigate the synergistic potential of halicin in combination with doxycycline (DOX).
• To assess the efficacy of halicin and DOX against enterococcal biofilms and in a murine infection model.

Main Methods:

• Minimum Inhibitory Concentration (MIC) determination.
• Checkerboard assay for synergistic effects.
• Biofilm inhibition and eradication assays.
• Scanning electron microscopy for cell membrane disruption.
• In vitro cytotoxicity assays and in vivo murine subcutaneous infection model.

Main Results:

• Halicin exhibited MIC values of 4–8 μg/ml against Enterococcus faecalis and Enterococcus faecium.
• A significant synergistic antibacterial effect was observed between halicin and DOX.
• The combination potently inhibited biofilm formation and eradicated preformed biofilms at sub-MIC levels.
• Halicin disrupted bacterial cell membranes at high concentrations.
• The halicin-DOX combination demonstrated low cytotoxicity and reduced bacterial load and inflammation in vivo without significant side effects.

Conclusions:

• Halicin possesses antimicrobial activity against clinically relevant Enterococcus strains.
• The combination of halicin and DOX exhibits synergistic activity, effectively targeting biofilms.
• Halicin and DOX present a promising therapeutic strategy for treating enterococcal infections with a favorable safety profile.