Cell death in Leishmania

Abstract

Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce numerous adverse effects and for which resistance is increasingly worrying. In this context, the particularly original organization of the Leishmania parasite in comparison to higher eukaryotes is a great advantage. It allows for the development of new, very specific, and thus non-cytotoxic treatments. Among these originalities, Leishmania cell death can be cited. Despite a classic pattern of apoptosis, key mammalian apoptotic proteins are not present in Leishmania, such as caspases, cell death receptors, and anti-apoptotic molecules. Recent studies have helped to develop a better understanding of parasite cell death, identifying new proteins or even new apoptotic pathways. This review provides an overview of the current knowledge on Leishmania cell death, describing its physiological roles and its phenotype, and discusses the involvement of various proteins: endonuclease G, metacaspase, aquaporin Li-BH3AQP, calpains, cysteine proteinase C, LmjHYD36 and Lmj.22.0600. From these data, potential apoptotic pathways are suggested. This review also offers tools to identify new Leishmania cell death effectors. Lastly, different approaches to use this knowledge for the development of new therapeutic tools are suggested: either inhibition of Leishmania cell death or activation of cell death for instance by treating cells with proteins or peptides involved in parasite death fused to a cell permeant peptide or encapsulated into a lipidic vector to target intra-macrophagic Leishmania cells.

A Betulinic Acid Derivative, BA5, Induces G0/G1 Cell Arrest, Apoptosis Like-Death, and Morphological Alterations in Leishmania sp

“…Because the formation of blebbing in the membrane, cell rounding, and flagella damage generally culminates in the formation of apoptotic bodies ( Basmaciyan and Casanova, 2019 ), we evaluated the mechanism by which compound BA5 could cause parasite death. Promastigotes were double-stained with Annexin-V-FITC and propidium iodide (PI) for flow cytometry analysis.…”

HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani

“…The viability and virulence of Leishmania parasites depend upon some key enzymes like metacaspase and PARP-1 (poly[ADP]-ribose polymerase-1) genes, compared to SIR2 (silent information regulator)-related proteins ( Sengupta et al., 2011 ; Mittal et al., 2017 ; Basmaciyan and Casanova, 2019 ). Stress-induced overexpression of PARP1 can lead to suppression of sirtuins (SIR2) via depletion of intracellular nicotine adenine dinucleotide (NAD) levels resulting in ATP depletion, DNA damage, and cell death in protozoan parasites ( Mittal et al., 2017 ).…”

Effect of serial photodynamic therapy with curcumin on Leishmania braziliensis and Leishmania amazonensis promastigotes

“…According to Basmaciyan & Casanova (2019), for apoptosis to be defined in Leishmania several criteria must be considered, and, in relation to morphology at least two of the following five alterations must be present: cell shrinkage, cell rounding, alterations in the plasma membrane with the maintenance of its integrity, nuclear fragment and chromatin condensation. By means of the experimental procedures outlined in this study it was possible to identify cell shrinkage and rounding in the two Leishmania species evaluated, thus suggesting that the use of PDT, more precisely sPDT was able to cause irreversible damage to the structure of these protozoa, probably by inducing apoptosis.…”

“…By means of the experimental procedures outlined in this study it was possible to identify cell shrinkage and rounding in the two Leishmania species evaluated, thus suggesting that the use of PDT, more precisely sPDT was able to cause irreversible damage to the structure of these protozoa, probably by inducing apoptosis. Also, according to Basmaciyan & Casanova (2019), the induction of oxidative stress with production of ROS promotes stimuli that induce phenotypes similar to apoptosis. These morphological changes were also reported in a study with curcumin and using fluence of 10 J.cm -2 carried out by Pinto et al (2016).…”