Repurposing ethyl bromopyruvate as a broad-spectrum antibacterial

Area of Science:

• Microbiology
• Drug Discovery
• Antimicrobial Resistance

Background:

• Drug-resistant bacteria, including Mycobacterium tuberculosis and ESKAPE pathogens, pose a significant threat to public health.
• Drug repurposing offers a rapid and effective strategy for identifying novel antibiotics.

Purpose of the Study:

• To evaluate ethyl bromopyruvate as a potential broad-spectrum antibacterial agent.
• To assess its efficacy against drug-susceptible and drug-resistant Mycobacterium tuberculosis and ESKAPE pathogens.

Main Methods:

• Growth inhibition assays were performed to determine the antibacterial activity of ethyl bromopyruvate.
• Time-kill kinetics, drug synergy, biofilm disruption, intracellular killing, and in vivo efficacy in a murine model were assessed.

Main Results:

• Ethyl bromopyruvate demonstrated equipotent broad-spectrum activity against M. tuberculosis and ESKAPE pathogens.
• It inhibited key metabolic enzymes like GAPDH and pyruvate kinase, leading to reduced ATP levels and iron uptake.
• Ethyl bromopyruvate effectively reduced bacterial biofilms and showed significant in vivo efficacy comparable to vancomycin at a lower dosage.

Conclusions:

• Ethyl bromopyruvate is identified as a potent broad-spectrum antibacterial agent with potential for treating infections caused by drug-resistant bacteria.
• Its efficacy in reducing bacterial load, inhibiting biofilms, and demonstrating in vivo activity supports its repositioning as a novel antibiotic.