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

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High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species. / Fehling, Helena; Niss, Hanno; Bea, Annika; Kottmayr, Nadine; Brinker, Christine; Hoenow, Stefan; Sellau, Julie; Gilberger, Tim-Wolf; Ting, Frederic; Landschulze, Dirk; Meier, Chris; Clos, Joachim; Lotter, Hannelore.

In: MICROORGANISMS, Vol. 9, No. 2, 422, 18.02.2021.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

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 2021, 'High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species', MICROORGANISMS, vol. 9, no. 2, 422. https://doi.org/10.3390/microorganisms9020422

APA

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. (2021). High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species. MICROORGANISMS, 9(2), [422]. https://doi.org/10.3390/microorganisms9020422

Vancouver

Bibtex

@article{1c6a89c38d2347a8a5a4950f615cdba1,
title = "High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species",
abstract = "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.",
author = "Helena Fehling and Hanno Niss and Annika Bea and Nadine Kottmayr and Christine Brinker and Stefan Hoenow and Julie Sellau and Tim-Wolf Gilberger and Frederic Ting and Dirk Landschulze and Chris Meier and Joachim Clos and Hannelore Lotter",
year = "2021",
month = feb,
day = "18",
doi = "10.3390/microorganisms9020422",
language = "English",
volume = "9",
journal = "MICROORGANISMS",
issn = "2076-2607",
publisher = "MDPI AG",
number = "2",

}

RIS

TY - JOUR

T1 - High Content Analysis of Macrophage-Targeting EhPIb-Compounds against Cutaneous and Visceral Leishmania Species

AU - Fehling, Helena

AU - Niss, Hanno

AU - Bea, Annika

AU - Kottmayr, Nadine

AU - Brinker, Christine

AU - Hoenow, Stefan

AU - Sellau, Julie

AU - Gilberger, Tim-Wolf

AU - Ting, Frederic

AU - Landschulze, Dirk

AU - Meier, Chris

AU - Clos, Joachim

AU - Lotter, Hannelore

PY - 2021/2/18

Y1 - 2021/2/18

N2 - 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.

AB - 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.

U2 - 10.3390/microorganisms9020422

DO - 10.3390/microorganisms9020422

M3 - SCORING: Journal article

C2 - 33670713

VL - 9

JO - MICROORGANISMS

JF - MICROORGANISMS

SN - 2076-2607

IS - 2

M1 - 422

ER -