Department of Parasitology, Instituto de Investigación Biosanitaria (ibs.Granada), Hospitales Universitarios De Granada/University of Granada, Severo Ochoa S/n, E-18071, Granada, Spain.
Department of Microbiology, Faculty of Sciences. C/ Fuentenueva S/n. University of Granada, Severo Ochoa /n, 18071, Granada, Spain.
Int J Parasitol Drugs Drug Resist. 2019 Aug;10:1-8. doi: 10.1016/j.ijpddr.2019.03.003. Epub 2019 Mar 29.
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.
克氏锥虫引起的恰加斯病是拉丁美洲的一个重大公共卫生问题,影响了全球约 800 万人。目前迫切需要确定新的抗恰加斯病药物,因为现有的唯一治疗选择硝呋莫司和苯并咪唑已使用了超过 40 年,且毒性高、疗效有限,在疾病的慢性阶段经常失败。最近,已有研究描述了肠球菌素 AS-48 对布氏锥虫和利什曼原虫属的抗寄生虫作用。在这项工作中,我们证明了 AS-48 细菌素对 T. cruzi 的体外潜力。有趣的是,AS-48 对不同 T. cruzi 株的三种形态均有更有效的作用,且比参考药物苯并咪唑的细胞毒性更低。此外,AS-48 符合作为潜在抗恰加斯病药物的标准,是一种很有前途的治疗替代方法。根据作用机制,AS-48 的杀锥虫活性可通过活性氧物质的产生和线粒体去极化来解释,导致快速而严重的生物能崩溃。