Graduate School of Pharmaceutical Sciences, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo 108–8641, Japan.
Biol Pharm Bull. 2012;35(1):48-53. doi: 10.1248/bpb.35.48.
Staphyloxanthin, a yellow pigment produced by methicillin-resistant Staphylococcus aureus (MRSA), is a virulent factor escaping from the host immune system. A new screening method for inhibitors of staphyloxanthin production by MRSA was established using paper disks. By this screening method, inhibitors of staphyloxanthin production were selected from the natural product library (ca. 300) and from actinomycete culture broths (ca. 1000). From the natural product library, four known inhibitors of lipid metabolism, cerulenin, dihydrobisvertinol, xanthohumol and zaragozic acid, were found to inhibit staphyloxanthin production; however, typical antibiotics used clinically, including vancomycin, had no effect on staphyloxanthin production. From actinomycete culture broths, two known anthraquinones, 6-deoxy-8-O-methylrabelomycin and tetrangomycin, were found to inhibit staphyloxanthin production by MRSA in the paper disk assay. These results suggested that this screening method is useful and effective to find compounds targeting staphyloxanthin production, leading to a new type of chemotherapeutics against MRSA infection.
金黄色素是耐甲氧西林金黄色葡萄球菌（MRSA）产生的一种黄色色素，是一种逃避宿主免疫系统的毒力因子。本文建立了一种使用纸片筛选 MRSA 金黄色素产生抑制剂的新方法。通过这种筛选方法，从天然产物文库（约 300 种）和放线菌培养物（约 1000 种）中筛选出了金黄色素产生抑制剂。从天然产物文库中发现了四种已知的脂代谢抑制剂，即杆菌肽、二氢双倍半萜醇、黄腐醇和扎拉格酸，它们能够抑制金黄色素的产生；然而，临床上常用的典型抗生素，如万古霉素，对金黄色素的产生没有影响。从放线菌培养物中发现了两种已知的蒽醌类化合物，即 6-去氧-8-O-甲基雷博霉素和四氮霉素，它们能够在纸片试验中抑制 MRSA 产生金黄色素。这些结果表明，该筛选方法对于寻找针对金黄色素产生的化合物是有用和有效的，可能为治疗耐甲氧西林金黄色葡萄球菌感染提供一种新的化疗药物。
