Repurposing Thiram and Disulfiram as Antibacterial Agents for Multidrug-Resistant Staphylococcus aureus Infections

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Multidrug-resistant Staphylococcus aureus poses a significant public health threat.
• Vancomycin is a critical antibiotic for treating S. aureus infections, but resistance is increasing.
• Novel antibacterial agents and strategies are urgently needed to combat resistant bacteria.

Purpose of the Study:

• To evaluate thiram and disulfiram as potential antibacterial agents against multidrug-resistant Staphylococcus aureus.
• To determine the spectrum of activity and mechanism of action of thiram and disulfiram.
• To investigate the potential of disulfiram to restore vancomycin susceptibility in resistant S. aureus strains.

Main Methods:

• Minimum Inhibitory Concentration (MIC90) determination against a panel of 30 S. aureus strains.
• Assessment of bacteriostatic and bactericidal activity.
• In vitro synergy studies evaluating disulfiram in combination with vancomycin.

Main Results:

• Thiram and disulfiram demonstrated antibacterial activity against multidrug-resistant S. aureus strains.
• MIC90 values were 4 μg/ml for thiram and 16 μg/ml for disulfiram.
• Both agents exhibited rapid-acting bacteriostatic effects with a Gram-positive spectrum.
• Disulfiram significantly increased vancomycin susceptibility in vitro against vancomycin-resistant S. aureus.

Conclusions:

• Thiram and disulfiram are effective antibacterial agents against multidrug-resistant Staphylococcus aureus.
• Disulfiram shows promise in combination therapy to overcome vancomycin resistance.
• Further research is warranted to explore the clinical application of these compounds.