Targeting catabolite control protein A from Staphylococcus aureus by auranofin

Abstract

The emergence of antibiotic-resistant Staphylococcus aureus poses a huge threat to public health. Therefore, novel strategy to overcome antibiotic resistance are urgently needed. Auranofin, a marketed metallodrug for rheumatoid arthritis, has been recognized as a promising agent against multiple clinical isolates of S. aureus. However, until now, its antibacterial mechanism is not well understood. Herein, we verify that the catabolite control protein A (CcpA) from S. aureus is an important target for auranofin. Auranofin can directly bind to CcpA via two cysteine residues. Importantly, both in vitro and animal infection models assays demonstrated that auranofin can disrupt the biological activity of CcpA, which attenuates bacteria growth, inhibits the secretion of toxin and enhance efficacy of aminoglycoside antibiotic. Together, these findings further revealed the bactericidal mechanism of auranofin against S. aureus.