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Evaluation of a New Topical Treatment for the Control of Cutaneous Leishmaniasis
Article

High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species

1
Department of Molecular Parasitology and Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
2
Leishmaniasis Group, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
3
Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany
4
Biology Department, Faculty of Sciences, Universität Hamburg, 22609 Hamburg, Germany
5
Department of Chemistry, Faculty of Sciences, Universität Hamburg, 20146 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: David S. Lindsay
Microorganisms 2021, 9(2), 422; https://doi.org/10.3390/microorganisms9020422
Received: 29 December 2020 / Revised: 31 January 2021 / Accepted: 12 February 2021 / Published: 18 February 2021
(This article belongs to the Special Issue Treatment of Leishmaniasis)
An immunostimulatory glycolipid molecule from the intestinal protozoan parasite Entamoeba histolytica (Eh) and its synthetic analogs derived from its phosphatidylinositol-b-anchor (EhPIb) previously showed considerable immunotherapeutic effects against Leishmania major infection in vitro and in vivo. Here, we describe a high content screening assay, based on primary murine macrophages. Parasites detection is based on a 90 kDA heat shock protein-specific staining, enabling the detection of several Leishmania species. We validated the assay using L. major, L. braziliensis, L. donovani, and L. infantum as well as investigated the anti-leishmanial activity of six immunostimulatory EhPIb-compounds (Eh-1 to Eh-6). Macrophages infected with dermotropic species were more sensitive towards treatment with the compounds as their viability showed a stronger reduction compared to macrophages infected with viscerotropic species. Most compounds caused a significant reduction of the infection rates and the parasite burdens depending on the infecting species. Only compound Eh-6 was found to have activity against all Leishmania species. Considering the challenges in anti-leishmanial drug discovery, we developed a multi-species screening assay capable of utilizing non-recombinant parasite strains, and demonstrated its usefulness by screening macrophage-targeting EhPIb-compounds showing their potential for the treatment of cutaneous and visceral leishmaniasis. View Full-Text
Keywords: Leishmania; immunotherapy; high content screening; macrophages; drug discovery Leishmania; immunotherapy; high content screening; macrophages; drug discovery
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MDPI and ACS Style

Fehling, H.; Niss, H.; Bea, A.; Kottmayr, N.; Brinker, C.; Hoenow, S.; Sellau, J.; Gilberger, T.-W.; Ting, F.; Landschulze, D.; Meier, C.; Clos, J.; Lotter, H. High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species. Microorganisms 2021, 9, 422. https://doi.org/10.3390/microorganisms9020422

AMA Style

Fehling H, Niss H, Bea A, Kottmayr N, Brinker C, Hoenow S, Sellau J, Gilberger T-W, Ting F, Landschulze D, Meier C, Clos J, Lotter H. High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species. Microorganisms. 2021; 9(2):422. https://doi.org/10.3390/microorganisms9020422

Chicago/Turabian Style

Fehling, Helena, Hanno Niss, Annika Bea, Nadine Kottmayr, Christine Brinker, Stefan Hoenow, Julie Sellau, Tim-Wolf Gilberger, Frederic Ting, Dirk Landschulze, Chris Meier, Joachim Clos, and Hannelore Lotter. 2021. "High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species" Microorganisms 9, no. 2: 422. https://doi.org/10.3390/microorganisms9020422

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