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Abstract

The protozoan parasites Leishmania, Trypanosoma cruzi and Trypanosoma brucei show multiple features consistent with a form of programmed cell death (PCD). Despite some similarities with apoptosis of mammalian cells, PCD in trypanosomatid protozoans appears to be significantly different. In these unicellular organisms, PCD could represent an altruistic mechanism for the selection of cells, from the parasite population, that are fit to be transmitted to the next host. Alternatively, PCD could help in controlling the population of parasites in the host, thereby increasing host survival and favoring parasite transmission, as proposed by Seed and Wenk. Therefore, PCD in trypanosomatid parasites may represent a pathway involved both in survival and propagation of the species.

Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death

“…A possible role of apoptosis in the biology of trypanosomatids would be to control parasite numbers in response to limited resources, or within the host for the perpetuation of the infection [191]. It could also be a useful mechanism to avoid an inflammatory response leading to killing of the entire parasite population [69,92].…”

Disuccinyl Betulin Triggers Metacaspase-Dependent Endonuclease G-Mediated Cell Death in Unicellular Protozoan Parasite Leishmania donovani

“…In Leishmania spp., PCD helps in altruistic growth control and organizes them into clonal populations (9) by (i) selecting for the fitter cells within the population, (ii) optimally regulating the cell number to adapt to the environmental constraints, and (iii) tightly controlling the cell cycle and cell differentiation. Topoisomerases are DNA manipulators that relieve the torsional strain in DNA that is built up during vital cellular processes.…”

N -Butyl-[1-(4-Methoxy)Phenyl-9 H -β-Carboline]-3-Carboxamide Prevents Cytokinesis in Leishmania amazonensis

“…␤-CB does not induce externalization of phosphatidylserine, disruption of the plasma membrane, and exacerbated autophagic process. To corroborate the hypothesis that ␤-CB prevents cytokinesis in L. amazonensis as a cytostatic and not a cytotoxic effect, certain alterations that characterize different cell death pathways were assessed, including externalization of phosphatidylserine in apoptotic cells, disruption of the plasma membrane in necrotic cells, and the presence of high numbers of autophagic vacuoles in cells that are suffering cell death by autophagy (15)(16)(17)(18). We performed flow cytometric analyses using PI labeling to identify cell membrane disruption and annexin V FITC labeling to investigate the externalization of phosphatidylserine.…”

“…Cell death pathways may be generally classified into apoptosis (i.e., programmed cell death characterized by cytoplasmic retraction, chromatin condensation, chromosomal DNA fragmentation, mitochondrial swelling, exposure of phosphatidylserine residues at the outer plasma membrane, and activation of caspases), necrosis (i.e., an unregulated process characterized by irreversible disruption of plasma membrane integrity, organ- elle breakdown, and randomly fragmented DNA), and exacerbation of the autophagic process, whereby cells remove or remodel damaged cell structures but under certain conditions can induce an intense cytoplasmic vacuolization and dismantling of the cellular organization, resulting in cell death (16)(17)(18). In order to determine the manner by which ␤-CB exerted its antiproliferative activity, we performed flow cytometry analyses using PI dye to identify cell membrane disruption (in necrotic cells) and annexin V FITC to investigate the externalization of phosphatidylserine, a typical feature of apoptotic cells (18). Treatment with crescent concentrations of ␤-CB did not alter the percentage of cells labeled with PI, demonstrating that the parasites did not suffer cell membrane damage and probably did not undergo a necrotic process.…”