Entomopathogenic bacteria Photorhabdus luminescens as drug source against Leishmania amazonensis
Entomopathogenic bacteria Photorhabdus luminescens as drug source against Leishmania amazonensis
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DOI：
10.1017/s0031182017002001
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发表时间：
2018-07-01
期刊：
影响因子：
2.4
通讯作者：
Da Silva, Onilda Santos
中科院分区：
文献类型：
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作者：
Antonello, Ana Maria;Sartori, Thais;Da Silva, Onilda Santos
利什曼病是一种广泛传播的人畜共患疾病，存在药物有效性低、寄生虫出现耐药性和严重不良反应等严重问题。近年来，昆虫致病细菌光habdus luminescens产生的次生代谢物引起了人们的广泛关注。在这里，我们评估了发光P.培养液的杀利什曼尼虫活性。首先，将亚马逊利什曼原虫的原鞭毛虫与无细胞条件培养液中培养，并监测寄生虫的存活情况。条件培养基的不同预处理表明，利什曼尼的活性是由于分泌小于3 kDa的肽。在条件培养基中富集光habdus-derived leishmanicidal toxin (PLT)，并测定其对promastigotes线粒体膜电位的影响。此外，还对PLT对无尾线虫的生物活性进行了评价。PLT能抑制亚马逊河蛭体的生长，并对亚马逊河蛭体的promastigoi和amastigoi表现出显著的利什曼尼杀虫活性。PLT在寄生虫中也引起线粒体功能障碍，但对哺乳动物细胞和人红细胞的毒性较低。此外，抗无尾螺旋体活性与一氧化氮的产生无关。综上所述，我们的研究结果表明，发光假单胞菌分泌的利什曼毒素肽(s)有望成为治疗利什曼病的新药。
Leishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions. In recent years, considerable attention has been given to secondary metabolites produced by Photorhabdus luminescens, an entomopathogenic bacterium. Here, we assessed the leishmanicidal activity of P. luminescens culture fluids. Initially, promastigotes of Leishmania amazonensis were incubated with cell free conditioned medium of P. luminescens and parasite survival was monitored. Different pre-treatments of the conditioned medium revealed that the leishmanicidal activity is due to a secreted peptide smaller than 3 kDa. The Photorhabdus-derived leishmanicidal toxin (PLT) was enriched from conditioned medium and its effect on mitochondrial membrane potential of promastigotes, was determined. Moreover, the biological activity of PLT against amastigotes was evaluated. PLT inhibited the parasite growth and showed significant leishmanicidal activity against promastigote and amastigotes of L. amazonensis. PLT also caused mitochondrial dysfunction in parasites, but low toxicity to mammalian cell and human erythrocytes. Moreover, the anti-amastigote activity was independent of nitric oxide production. In summary, our results highlight that P. luminescens secretes Leishmania-toxic peptide(s) that are promising novel drugs for therapy against leishmaniasis.