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 μM) 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.

Staphyloxanthin（STX）是由金黄色葡萄球菌（S. aureus）产生的毒力因子，包括耐甲氧西林的金黄色葡萄球菌（MRSA），这是一种广泛分布的革兰氏阳性细菌，与几种临床人类感染有关。我们在本文中报道了广谱抗真菌剂萘替芬在金黄色葡萄球菌的光动力抗微生物治疗（PACT）中起着重要作用。STX以剂量依赖的方式减弱了对金黄色葡萄球菌的PACT效应，这可能是由于其清除活性氧（ROS）的生物学功能。相反，金黄色葡萄球菌的敏感性与未用萘替芬治疗的金黄色葡萄球菌相比，用萘替芬（10μM）孵育后对PACT的抵抗力明显改善。产生这种现象的原因是，萘替芬抑制STX生物合成并提高膜通透性。两者合计，我们确定STX是金黄色葡萄球菌中PACT的限制因素。同时，我们发现PACT与STX生物合成抑制剂Naftifine的组合对金黄色葡萄球菌具有协同抗菌作用，为快速有效治疗金黄色葡萄球菌感染而无耐药性提供了新途径。