Antibacterial and antivirulence activities of auranofin against Clostridium difficile

Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last two decades, C. difficile infections (CDIs) have become a national concern because of the emergence of hypervirulent mutants with increased capability to produce toxins and spores. This has resulted in an increased number of infections and deaths associated with CDI. The scarcity of anticlostridial drugs has led to unsatisfactory cure rates, elevated recurrence rates and permitted enhanced colonization with other drug-resistant pathogens (such as vancomycin-resistant enterococci) in afflicted patients. Therefore, both patients and physicians are facing an urgent need for more effective therapies to treat CDI. In an effort to find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral antirheumatic drug that has recently been found to possess antibacterial activity. Auranofin exhibited potent activity against C. difficile isolates, inhibiting growth at a concentration of 1 µg/mL against 50% of all tested isolates. Auranofin inhibited both toxin production and spore formation, a property lacking in both vancomycin and metronidazole (the primary agents used to treat CDI). Auranofin had a direct protective activity against C. difficile toxin-mediated inflammation and inhibited the growth of vancomycin-resistant enterococci. Auranofin is a promising candidate that warrants further investigation as a treatment option for C. difficile infections.