Murine infection with bioluminescent Leishmania infantum axenic amastigotes applied to drug discovery

• Published in: Scientific reports Vol. 9; no. 1; pp. 18989 - 8
• Main Authors: Mendes Costa, David, Cecílio, Pedro, Santarém, Nuno, Cordeiro-da-Silva, Anabela, Tavares, Joana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-12-2019; Nature Publishing Group
• Subjects: 59; 59/5; 64; 64/60; 692/308/1426; 692/699/255/1715; Amastigotes; Animals; Axenic Culture; Bioluminescence; Drug Discovery; Humanities and Social Sciences; Leishmania; Leishmania infantum; Leishmania infantum - pathogenicity; Luciferases - metabolism; Luminescence; Mice, Inbred BALB C; multidisciplinary; Parasites; Parasites - pathogenicity; Science; Science (multidisciplinary); Tropical diseases; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• 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.