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Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium |
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| Authors: | Gundula Min-Oo Silayuv E. Bongfen Irena Radovanovic Helton Santiago Antonio Gigliotti Rothfuchs Alan Sher Anny Fortin Kevin C. Kain |
| Affiliation: | a Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Room 910, Montréal, QC, Canada H3G 1Y6 b McLaughlin-Rotman Centre for Global Health, UHN, Department of Medicine and McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Canada c Montreal General Hospital Research Institute, Montreal, Canada d Department of Microbiology, Immunology and Tropical Medicine, George Washington University Health Center, Washington, DC, USA e Laboratory of Parasitic Diseases, NIH, Bethesda, MD, USA f Laboratory of Molecular Immunology National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA g Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada |
| Abstract: | In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection. |
| Keywords: | Apicomplexa Plasmodium Cysteamine Mouse model Anti-parasitic |
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