Naftifine enhances photodynamic therapy against Staphylococcus aureus by inhibiting staphyloxanthin expression

Staphyloxanthin (STX) is a virulence factor produced by Staphylococcus aureus (S. aureus) including methicillin-resistant S. aureus (MRSA), a widely distributed Gram-positive bacterium related to several clinical human infections. We herein reported that Naftifine, a broad-spectrum antifungal agent, plays an important role on photodynamic antimicrobial therapy (PACT) for S. aureus. STX attenuated the PACT effect on S. aureus in a dose-dependent manner, which probably due to its biological function of scavenging reactive oxygen species (ROS). On the contrary, the sensitivity of S. aureus to PACT was significantly improved after an incubation with Naftifine (10 mu M) compared with that of S. aureus untreated with Naftifine. The reason for this phenomenon is that Naftifine inhibits STX biosynthesis and improves membrane permeability. Taken together, we identified STX as a limiting factor of PACT in S. aureus. Meanwhile, we found that the combination of PACT and Naftifine, an inhibitor of STX biosynthesis, has synergistic antibacterial effect on S. aureus, and provide a new way for the rapid and efficient treatment of S. aureus infection without drug resistance.