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评估阳离子抗菌肽 dermaseptin 01 对曼氏血吸虫的体外活性。

Evaluation of the in vitro activity of dermaseptin 01, a cationic antimicrobial peptide, against Schistosoma mansoni.

机构信息

Laboratório de Parasitologia, Instituto Butantan, Avenida Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.

出版信息

Chem Biodivers. 2011 Mar;8(3):548-58. doi: 10.1002/cbdv.201000163.

Abstract

Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of dermaseptin 01 (DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, on Schistosoma mansoni adult worms. DS 01 at a concentration of 100 μg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 μg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50-200 μg/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a dermaseptin.

摘要

血吸虫病是一种被忽视的热带病,仍然是全球范围内一个相当严重的公共卫生问题。由于血吸虫病控制的主要手段是使用单一药物吡喹酮进行化学疗法,因此药物耐药性令人担忧。在这里,我们研究了在皮肤分泌物中发现的抗菌肽 dermaseptin 01(DS 01)对曼氏血吸虫成虫的体外作用。DS 01 在浓度为 100μg/ml 时,可降低虫体的运动活性,并在 RPMI 1640 培养基中在 48 小时内导致所有虫体死亡。在最高亚致死浓度的抗菌肽(75μg/ml)下,观察到配对雌性蠕虫的产卵量减少了 100%。此外,DS 01 诱导了曼氏血吸虫表皮的形态改变,通过共聚焦显微镜进行的定量分析显示,在 50-200μg/ml 的浓度范围内,结节的广泛破坏呈剂量依赖性。这是首次报道 dermaseptin 对血吸虫具有驱虫活性。

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