Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis

TLDR

The growing threat of drug‑resistant infections creates an urgent need for new antibiotics with novel mechanisms, and the FDA‑approved status of auranofin may expedite its clinical deployment. Auranofin targets thioredoxin reductase, an enzyme not inhibited by other antibiotics, enabling activity against diverse drug‑resistant strains in vitro and in a mouse infection model. Auranofin demonstrates potent bactericidal activity against Gram‑positive pathogens and is a promising candidate for antibacterial drug repurposing.

Abstract

Significance The identification of new antibiotics with novel mechanisms of action has become a pressing need considering the growing threat of drug-resistant infections. We have identified auranofin, an FDA-approved drug, as having potent bactericidal activity against Gram-positive pathogenic bacteria. Auranofin inhibits an enzyme, thioredoxin reductase, not targeted by other antibiotics, and thus retains efficacy against many clinically relevant drug-resistant strains, including in a mouse model of infection. Because auranofin is an approved drug, its route to the clinic may be expedited with reduced cost. Our work suggests that auranofin is a candidate for drug repurposing in antibacterial therapy.