Abstract:
BACKGROUND:Visceral leishmaniasis is a neglected parasitic disease with no vaccine available and its pharmacological treatment is reduced to a limited number of unsafe drugs. The scarce readiness of new antileishmanial drugs is even more alarming when relapses appear or the occurrence of hard-to-treat resistant strains is detected. In addition, there is a gap between the initial and late stages of drug development, which greatly delays the selection of leads for subsequent studies. METHODOLOGY/PRINCIPAL FINDINGS:In order to address these issues, we have generated a red-shifted luminescent Leishmania infantum strain that enables long-term monitoring of parasite burden in individual animals with an in vivo limit of detection of 106 intracellular amastigotes 48 h postinfection. For this purpose, we have injected intravenously different infective doses (104-5x108) of metacyclic parasites in susceptible mouse models and the disease was monitored from initial times to 21 weeks postinfection. The emission of light from the target organs demonstrated the sequential parasite colonization of liver, spleen and bone marrow. When miltefosine was used as proof-of-concept, spleen weight parasite burden and bioluminescence values decreased significantly. CONCLUSIONS:In vivo bioimaging using a red-shifted modified Leishmania infantum strain allows the appraisal of acute and chronic stage of infection, being a powerful tool for accelerating drug development against visceral leishmaniasis during both stages and helping to bridge the gap between early discovery process and subsequent drug development.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Álvarez-Velilla R,Gutiérrez-Corbo MDC,Punzón C,Pérez-Pertejo MY,Balaña-Fouce R,Fresno M,Reguera RMdoi
10.1371/journal.pntd.0007133subject
Has Abstractpub_date
2019-02-14 00:00:00pages
e0007133issue
2eissn
1935-2727issn
1935-2735pii
PNTD-D-18-00984journal_volume
13pub_type
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