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Insights into Chagas treatment based on the potential of bacteriocin AS-48.
International Journal for Parasitology: Drugs and Drug Resistance ( IF 4 ) Pub Date : 2019-03-29 , DOI: 10.1016/j.ijpddr.2019.03.003
Rubén Martín-Escolano 1 , Rubén Cebrián 2 , Javier Martín-Escolano 1 , Maria J Rosales 1 , Mercedes Maqueda 2 , Manuel Sánchez-Moreno 1 , Clotilde Marín 1
Affiliation  

Chagas disease caused by the protozoan parasite Trypanosoma cruzi represents a significant public health problem in Latin America, affecting around 8 million cases worldwide. Nowadays is urgent the identification of new antichagasic agents as the only therapeutic options available, Nifurtimox and Benznidazole, are in use for >40 years, and present high toxicity, limited efficacy and frequent treatment failures in the chronic phase of the disease. Recently, it has been described the antiparasitic effect of AS-48, a bacteriocin produced by Enterococcus faecalis, against Trypanosoma brucei and Leishmania spp. In this work, we have demonstrated the in vitro potential of the AS-48 bacteriocin against T. cruzi. Interesting, AS-48 was more effective against the three morphological forms of different T. cruzi strains, and displayed lower cytotoxicity than the reference drug Benznidazole. In addition, AS-48 combines the criteria established as a potential antichagasic agent, resulting in a promising therapeutic alternative. According to the action mechanism, AS-48 trypanocidal activity could be explained in a mitochondrion-dependent manner through a reactive oxygen species production and mitochondrial depolarization, causing a fast and severe bioenergetic collapse.

中文翻译:

根据细菌素AS-48的潜力深入了解Chagas治疗。

由原生动物寄生虫克氏锥虫引起的南美锥虫病在拉丁美洲代表着重大的公共卫生问题,全球影响约800万例。如今,迫切需要鉴定新的抗chachagic药物作为唯一可用的治疗选择,Nifurtimox和Benznidazole的使用已超过40年,并且在该疾病的慢性期表现出高毒性,有限的疗效和频繁的治疗失败。最近,已经描述了由粪肠球菌产生的细菌素AS-48对布鲁氏锥虫和利什曼原虫属的抗寄生虫作用。在这项工作中,我们已经证明了AS-48细菌素对克氏锥虫的体外潜力。有趣的是,AS-48可以更有效地对抗不同的克鲁氏梭菌菌株的三种形态学形式,并显示出比参考药物苄硝唑更低的细胞毒性。此外,AS-48结合了确立为潜在抗chachaicant剂的标准,从而带来了有希望的治疗选择。根据作用机理,可以通过产生活性氧和线粒体去极化来以线粒体依赖的方式解释AS-48锥虫活性,从而引起快速而严重的生物能崩溃。
更新日期:2019-11-01
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