Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery
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DOI：
10.1038/s41598-019-55474-3
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发表时间：
2019-12-12
影响因子：
4.6
通讯作者：
Tavares, Joana
中科院分区：
文献类型：
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作者：
Costa, David Mendes;Cecilio, Pedro;Tavares, Joana
利什曼病是由利什曼原虫引起的一种重要的媒介传播的被忽视的热带疾病。目前的抗利什曼病化疗并不令人满意，这证明继续寻找替代治疗方案是合理的。在这里，我们证明了表达荧光素酶的婴儿无性利什曼原虫，不同于前鞭毛体，对BALB/c小鼠具有高度的感染性，从而在感染后两周就在靶器官如肝脏和脾产生强烈的生物发光信号。用参比药物两性霉素B和米替福辛治疗在减少寄生虫负担方面有效。这种模型允许使用全鼠生物发光成像来评估治疗效果，而不需要等待几周才能通过这种非侵入性方法检测到脾感染。总之，我们建议在一种初步的方法中使用该模型来评估有希望的化学实体的治疗效果，而不必牺牲大量动物或等待数天的读数。
Leishmaniasis is an important vector-borne neglected tropical disease caused by Leishmania parasites. Current anti-Leishmania chemotherapy is unsatisfactory, justifying the continued search for alternative treatment options. Herein, we demonstrate that luciferase-expressing Leishmania infantum axenic amastigotes, unlike promastigotes, are highly infectious to BALB/c mice and thus generate a robust bioluminescent signal in target organs, such as the liver and the spleen, as early as two weeks after infection. Treatment with the reference drugs amphotericin B and miltefosine was effective at reducing parasite burdens. This model allows the assessment of treatment efficacy using whole-mouse bioluminescence imaging without the need to wait several weeks for spleen infections to be detectable by this non-invasive method. In conclusion, we propose the use of this model in an initial approach to evaluate the treatment efficacy of promising chemical entities without having to sacrifice large numbers of animals or to wait several days for a readout.