Infectivity and Drug Susceptibility Profiling of Different Leishmania-Host Cell Combinations
| Autor: | Eric Prina, Laura Piel, Joo Hwan No, Thibault Rosazza, Gerald F. Späth, Kyung-Hwa Baek |
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| Přispěvatelé: | Leishmania Lab [Corée du sud], Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Research Foundation of Korea (NRF-2017M3A9G6068246 and 2017R1D1A1B03033204) through a grant funded by the government of the Republic of Korea (MSIP) and Gyeonggi-do, and by the International Division of Institut Pasteur (PTR593), We thank Pascale Pescher from Institut Pasteur at Paris and Jean-Robert Ioset from the Drugs for Neglected Diseases initiative (DNDi) for providing critical comments on the manuscript., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Sodium stibogluconate 030106 microbiology Leishmania donovani lcsh:Medicine drugs susceptibility Microbiology 03 medical and health sciences parasitic diseases medicine Immunology and Allergy primary bone marrow-derived macrophage THP1 cell line [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Acute monocytic leukemia Amastigote Molecular Biology Infectivity Miltefosine General Immunology and Microbiology biology Leishmania amazonensis lcsh:R Leishmaniasis medicine.disease biology.organism_classification 3. Good health 030104 developmental biology Infectious Diseases THP-1 medicine.drug |
| Zdroj: | Pathogens Pathogens, MDPI, 2020, 9 (5), pp.393. ⟨10.3390/pathogens9050393⟩ Pathogens, 2020, 9 (5), pp.393. ⟨10.3390/pathogens9050393⟩ Pathogens, Vol 9, Iss 393, p 393 (2020) Volume 9 Issue 5 |
| ISSN: | 2076-0817 |
| Popis: | Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a spectrum of a disease that threatens public health worldwide. Although next-generation therapeutics are urgently needed, the early stage of the drug discovery process is hampered by very low hit rates from intracellular Leishmania phenotypic high-throughput screenings. Designing and applying a physiologically relevant in vitro assay is therefore in high demand. In this study, we characterized the infectivity, morphology, and drug susceptibility of different Leishmania and host cell infection combinations. Primary bone marrow-derived macrophage (BMDM) and differentiated human acute monocytic leukemia (THP-1) cells were infected with amastigote or promastigote forms of Leishmania amazonensis and Leishmania donovani. Regardless of host cell types, amastigotes were generally well phagocytosed and showed high infectivity, whereas promastigotes, especially those of L. donovani, had predominantly remained in the extracellular space. In the drug susceptibility test, miltefosine and sodium stibogluconate (SSG) showed varying ranges of activity with 14 and > 10-fold differences in susceptibility, depending on the host-parasite pairs, indicating the importance of assay conditions for evaluating antileishmanial activity. Overall, our results suggest that combinations of Leishmania species, infection forms, and host cells must be carefully optimized to evaluate the activity of potential therapeutic compounds against Leishmania. |
| Databáze: | OpenAIRE |
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