i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Sci Rep. 2019 Dec 12;9(1):18989. doi: 10.1038/s41598-019-55474-3.
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.
利什曼病是一种重要的经媒介传播的被忽视热带病，由利什曼原虫寄生虫引起。目前的抗利什曼原虫化疗效果并不令人满意，这证明了仍有必要寻找替代的治疗选择。在此，我们证明表达荧光素酶的利什曼原虫婴儿无鞭毛体与前鞭毛体不同，对 BALB/c 小鼠具有高度传染性，因此在感染后两周内，即使在肝脏和脾脏等靶器官中，也能产生强烈的生物发光信号。用参考药物两性霉素 B 和米替福新进行治疗可有效降低寄生虫负担。该模型允许使用全鼠生物发光成像来评估治疗效果，而无需等待数周才能通过这种非侵入性方法检测脾脏感染。总之，我们建议在初步评估有前途的化学实体的治疗效果时使用该模型，而无需牺牲大量动物或等待数天才能获得结果。
