The Auranofin-Colistin Combination Efficiency Against the Gram-Negative Strains: A Review.

Multidrug-resistant bacteria that possess resistance genes against last-resort antibiotics, such as colistin, are notably prevalent in hospital environments. Therapeutic options for addressing these infections are limited, prompting researchers to explore alternative strategies. One promising approach is drug repurposing, which involves testing combinations of antibiotics with other medications to discover potential synergistic effects against multidrug-resistant (MDR) strains. Auranofin, an antirheumatic drug known for its anti-inflammatory and antineoplastic properties, has recently been investigated in combination with colistin as a potential therapeutic strategy for treating infections caused by multidrug-resistant bacteria. A review of 10 articles retrieved from five public scientific databases indicates that all authors reported synergistic activity of the auranofin-colistin combination against multidrug-resistant (MDR) species, with effectiveness demonstrated in both in vitro and in vivo experiments. However, the minimal inhibitory concentrations (MICs) of this combination vary, and the precise mechanism of action remains unclear. Recent studies examining the crystal structure of metallo-beta-lactamase type 2 (NDM-1) and a probable phosphatidylethanolamine transferase, MCR-1 (which confers mobilized colistin resistance), suggest that activation with glutathione or N-acetylcysteine is necessary for efficacy. Additionally, there is strong evidence indicating that auranofin acts as a dual inhibitor of both MCR and metallo-beta-lactamase (MBL) by displacing the Zn(II) cofactor.