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

• Published in: Microorganisms (Basel) 2021-02, Vol.9 (2)
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 2076-2607

An immunostimulatory glycolipid molecule from the intestinal protozoan parasite ( ) and its synthetic analogs derived from its phosphatidylinositol-b-anchor ( PIb) previously showed considerable immunotherapeutic effects against 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 species. We validated the assay using , , and as well as investigated the anti-leishmanial activity of six immunostimulatory PIb-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 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 PIb-compounds showing their potential for the treatment of cutaneous and visceral leishmaniasis.