Abstract
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.
Highlights
Leishmaniasis is a neglected tropical disease, caused by Leishmania spp., flagellated protozoan parasites belonging to the family Trypanosomatidae [1,2]
We introduce an inducible suicidal system in Leishmania mexicana, a causative agent of cutaneous leishmaniasis
Growth kinetics was measured for five transgenic L. mexicana cell lines, expressing α-toxin, Cecropin-A, Attacin-A, BnSP-7, and Cathelicidin-5, in the presence or absence of the toxin stabilizers, TMP or TMP-lac
Summary
Leishmaniasis is a neglected tropical disease, caused by Leishmania spp., flagellated protozoan parasites belonging to the family Trypanosomatidae [1,2]. Pathogens 2020, 9, 79 trials based on killed or heat-inactivated parasites, recombinant proteins, and DNA vaccines have shown limitations in murine models and field studies [11]. Another promising experimental approach to this problem is a usage of the genetically modified Leishmania lines as attenuated vaccines [12,13,14,15,16]. We believe that the suicidal system presented here and the resultant of strongly attenuated parasites can be used to develop a novel vaccination strategy against L. mexicana, and provide additional insights into the host-derived immune response after elimination of the pathogen. We acknowledge that our findings must be properly reexamined in vivo in animal models of leishmaniasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
