Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens

Area of Science:

• Microbiology
• Pharmacology
• Drug Discovery

Background:

• The rise of multidrug-resistant (MDR) pathogens necessitates novel antimicrobial strategies.
• Developing new antimicrobials is costly and time-consuming, highlighting the value of drug repurposing.

Purpose of the Study:

• To evaluate the antimicrobial potential of ebselen, an organoselenium molecule, against MDR Gram-positive pathogens.
• To compare ebselen's efficacy with existing antibiotics like vancomycin and linezolid.

Main Methods:

• Assessed ebselen's activity against clinical isolates of Staphylococcus, Streptococcus, and Enterococcus.
• Determined minimum inhibitory concentrations (MIC90) and evaluated intracellular pathogen clearance.
• Investigated ebselen's mechanism of action, in vivo efficacy in a Caenorhabditis elegans model, and synergistic effects with conventional antimicrobials.

Main Results:

• Ebselen exhibited potent activity against MDR Gram-positive pathogens, surpassing vancomycin and linezolid.
• MIC90 values for ebselen were 0.5 mg/L for Enterococcus and 0.25 mg/L for Staphylococcus.
• Ebselen demonstrated significant clearance of intracellular methicillin-resistant Staphylococcus aureus (MRSA) and showed synergistic activity with existing antibiotics.

Conclusions:

• Ebselen is a promising candidate for treating MDR Gram-positive bacterial infections due to its potent activity and safety profile.
• Ebselen's ability to inhibit bacterial translation and its efficacy in vivo warrant further clinical evaluation.
• Drug repurposing of ebselen offers a viable strategy to combat the growing threat of antimicrobial resistance.