Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection

Siew Ling Choy, Hannah Bernin, Toshihiko Aiba, Eugenia Bifeld, Sarah Corinna Lender, Melina Mühlenpfordt, Jill Noll, Julia Eick, Claudia Marggraff, Hanno Niss, Nestor González Roldán, Shinji Tanaka, Masato Kitamura, Koichi Fukase, Joachim Clos, Egbert Tannich, Yukari Fujimoto, Hannelore Lotter

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Abstract

Intracellular pathogens belonging to the genus Leishmania have developed effective strategies that enable them to survive within host immune cells. Immunostimulatory compounds that counteract such immunological escape mechanisms represent promising treatment options for diseases. Here, we demonstrate that a lipopeptidephosphoglycan (LPPG) isolated from the membrane of a protozoan parasite, Entamoeba histolytica (Eh), shows considerable immunostimulatory effects targeted against Leishmania (L.) major, a representative species responsible for cutaneous leishmaniasis (CL). Treatment led to a marked reduction in the number of intracellular Leishmania parasites in vitro, and ameliorated CL in a mouse model. We next designed and synthesized analogs of the phosphatidylinositol anchors harbored by EhLPPG; two of these analogs reproduced the anti-leishmanial activity of the native compound by inducing production of pro-inflammatory cytokines. The use of such compounds, either alone or as a supportive option, might improve the currently unsatisfactory treatment of CL and other diseases caused by pathogen-manipulated immune responses.

Original languageEnglish
Article number9472
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Choy, S. L., Bernin, H., Aiba, T., Bifeld, E., Lender, S. C., Mühlenpfordt, M., Noll, J., Eick, J., Marggraff, C., Niss, H., Roldán, N. G., Tanaka, S., Kitamura, M., Fukase, K., Clos, J., Tannich, E., Fujimoto, Y., & Lotter, H. (2017). Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection. Scientific Reports, 7(1), [9472]. https://doi.org/10.1038/s41598-017-09894-8