Microbiology and Virology Unit, School of Medicine, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PL, UK.
J Antimicrob Chemother. 2013 Oct;68(10):2269-73. doi: 10.1093/jac/dkt195. Epub 2013 May 27.
Epidermicin is a novel antimicrobial peptide that has potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, and it may have potential for use in therapy for infections caused by these bacteria, though in vivo efficacy needs to be demonstrated. Galleria mellonella larvae have recently been introduced as an alternative in vivo model to mammalian systems and here we examined the ability of a synthetic version of epidermicin to protect G. mellonella larvae from infection with S. aureus strains.
G. mellonella larvae were infected with ∼2.5 × 10(6) cells per larva and then treated with vancomycin or epidermicin and survival recorded over a 120 h period. Vancomycin was used at up to 50 mg/kg and epidermicin at up to 200 mg/kg with administration of treatments occurring 0-2 h post-infection.
Epidermicin was shown to be non-toxic and did not stimulate the G. mellonella immune system. When administered 2 h post-infection at a maximum dose of 200 mg/kg, epidermicin significantly increased survival in larvae; however, altering the dosage regimen by reducing the time to administration to 30 min post-infection increased the potency of the peptide.
This is the first report of antimicrobial activity of an artificially synthesized peptide from the type IIc bacteriocin family. The novel peptide protects G. mellonella larvae from infection with both methicillin-susceptible and -resistant S. aureus, although the pharmacodynamic properties are not yet optimal.
表皮素是一种新型的抗菌肽,对革兰氏阳性病原体具有强大的活性,包括耐甲氧西林金黄色葡萄球菌,并且它可能有潜力用于治疗由这些细菌引起的感染,尽管需要在体内证明其疗效。最近,家蚕幼虫被引入作为哺乳动物系统的替代体内模型,我们在此研究了一种表皮素的合成版本保护家蚕幼虫免受金黄色葡萄球菌菌株感染的能力。
用约 2.5×10(6)个细胞/幼虫感染家蚕幼虫,然后用万古霉素或表皮素处理,并在 120 小时内记录存活情况。万古霉素的用量高达 50mg/kg,表皮素的用量高达 200mg/kg,治疗在感染后 0-2 小时进行。
表皮素显示无毒性,并且不会刺激家蚕幼虫的免疫系统。当在感染后 2 小时以最大剂量 200mg/kg 给药时,表皮素显著增加了幼虫的存活率;然而,通过将给药时间缩短至感染后 30 分钟,改变剂量方案增加了肽的效力。
这是首次报道人工合成的 IIc 型细菌素家族的抗菌肽具有抗菌活性。这种新型肽可保护家蚕幼虫免受耐甲氧西林和敏感的金黄色葡萄球菌感染,尽管药效学特性尚未最佳。