Leishmania are obligate intracellular parasites known to have developed successful ways of efficient immunity evasion. Because of this, leishmaniasis, a disease caused by these flagellated protists, is ranked as one of the most serious tropical infections worldwide. Neither prophylactic medication, nor vaccination has been developed thus far, even though the infection has usually led to strong and long-lasting immunity. In this paper, we describe a "suicidal" system established in Leishmania mexicana, a human pathogen causing cutaneous leishmaniasis. This system is based on the expression and (de)stabilization of a basic phospholipase A2 toxin from the Bothrops pauloensis snake venom, which leads to the inducible cell death of the parasites in vitro. Furthermore, the suicidal strain was highly attenuated during macrophage infection, regardless of the toxin stabilization. Such a deliberately weakened parasite could be used to vaccinate the host, as its viability is regulated by the toxin stabilization, causing a profoundly reduced pathogenesis.

Biology Centre Institute of Parasitology Czech Academy of Sciences 370 05 České Budějovice Czech Republic

Department of Parasitology Faculty of Science Charles University 128 44 Prague Czech Republic

Faculty of Sciences University of South Bohemia 370 05 České Budějovice Czech Republic

Life Science Research Centre and Institute of Environmental Technologies Faculty of Science University of Ostrava 710 00 Ostrava Czech Republic

Martsinovsky Institute of Medical Parasitology Tropical and Vector Borne Diseases Sechenov University 119435 Moscow Russia

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