Fujiyuki T, Imamura K, Hamamoto H, Sekimizu K
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Drug Discov Ther. 2010 Oct;4(5):349-54.
The therapeutic effect of dye compounds with antibacterial activity was evaluated in a silkworm model of Staphylococcus aureus infection. Among 13 chromogenic agents that show antibacterial activity against S. aureus (MIC = 0.02 to 19 μg/mL), rifampicin had a therapeutic effect. The ED(50) value in the silkworm model was consistent with that in a murine model. Other 12 dyes did not increase survival of the infected silkworms. We examined the reason for the lack of therapeutic efficacy. Amidol, pyronin G, and safranin were toxic to silkworms, which explained the lack of therapeutic effects. Fuchsin basic and methyl green disappeared quickly from the hemolymph after injection, suggesting that they are not stable in the hemolymph. Although coomassie brilliant blue R250/G250, cresyl blue, and nigrosin showed no toxic effects or instability in the hemolymph, they also did not have a therapeutic effect. The in vitro antibacterial actions of these dyes were inhibited by silkworm plasma or bovine serum albumin and filtration experiments demonstrated that cresyl blue bound to plasma proteins in the silkworm, suggesting that plasma protein binding inhibited the therapeutic efficacy of these four dyes. These findings indicate that drug screening using the silkworm infection model is useful for evaluating toxicity and pharmacokinetics of potential antibiotics.
在金黄色葡萄球菌感染的家蚕模型中评估了具有抗菌活性的染料化合物的治疗效果。在对金黄色葡萄球菌具有抗菌活性（MIC = 0.02至19μg/mL）的13种显色剂中，利福平具有治疗效果。家蚕模型中的ED(50)值与小鼠模型中的一致。其他12种染料并未提高感染家蚕的存活率。我们研究了缺乏治疗效果的原因。阿米酚、焦宁G和番红对家蚕有毒，这解释了缺乏治疗效果的原因。碱性品红和甲基绿注射后在血淋巴中迅速消失，表明它们在血淋巴中不稳定。尽管考马斯亮蓝R250/G250、甲酚蓝和nigrosin在血淋巴中未显示出毒性作用或不稳定性，但它们也没有治疗效果。这些染料的体外抗菌作用受到家蚕血浆或牛血清白蛋白的抑制，过滤实验表明甲酚蓝与家蚕血浆蛋白结合，表明血浆蛋白结合抑制了这四种染料的治疗效果。这些发现表明，使用家蚕感染模型进行药物筛选有助于评估潜在抗生素的毒性和药代动力学。
