The scourge of multidrug-resistant
bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new
antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional
antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an
antirheumatic drug,
auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that
auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including
meticillin-resistant S. aureus (MRSA),
vancomycin-intermediate S. aureus (VISA) and
vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625μg/mL to 0.125μg/mL. In vivo, topical
auranofin proved superior to conventional antimicrobials, including
fusidic acid and
mupirocin, in reducing the mean bacterial load in infected
wounds in a murine model of MRSA skin
infection. In addition to reducing the bacterial load, topical treatment of
auranofin greatly reduced the production of inflammatory
cytokines, including tumour
necrosis factor-α (TNFα),
interleukin-6 (IL-6),
interleukin-1 beta (IL-1β) and
monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover,
auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials
linezolid and
vancomycin. Taken together, these results support that
auranofin has potential to be repurposed as a topical
antimicrobial agent for the treatment of staphylococcal skin and
wound infections.