Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Éminences Grises”?

This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together

Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi

Lysosomal cysteine proteases from mammalian cells and plants are regulated by endogenous tight-binding inhibitors from the cystatin superfamily. The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cysteine proteases and may also count on endogenous inhibitors to regulate cellular proteolysis. Trypanosoma cruzi, the causative agent of Chagas heart disease, is a relevant model to explore this possibility because these intracellular parasites rely on their major lysosomal cysteine protease (cruzipain) to invade and multiply in mammalian host cells. Here we report the isolation, biochemical characterization, developmental stage distribution and subcellular localization of chagasin, an endogenous cysteine protease inhibitor in T. cruzi. We used high temperature induced denaturation to isolate a heat-stable cruzipain-binding protein (apparent molecular mass, 12 kDa) from epimastigote lysates. This protein was subsequently characterized as a tight-binding and reversible inhibitor of papain-like cysteine proteases. Immunoblotting indicated that the expression of chagasin is developmentally regulated and inversely correlated with that of cruzipain. Gold-labeled antibodies localized chagasin to the flagellar pocket and cytoplasmic vesicles of trypomastigotes and to the cell surface of amastigotes. Binding assays performed by probing living parasites with fluorescein (FITC)-cruzipain or FITC-chagasin revealed the presence of both inhibitor and protease at the cell surface of amastigotes. The intersection of chagasin and cruzipain trafficking pathways may represent a checkpoint for downstream regulation of proteolysis in trypanosomatid protozoa

DETC Induces Leishmania Parasite Killing in Human In Vitro and Murine In Vivo Models: A Promising Therapeutic Alternative in Leishmaniasis

Background: Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings: We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p,0.001) and is able to ??????sterilize?????? Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p,0.001) and parasite destruction (p,0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p,0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection

Interference with Hemozoin Formation Represents an Important Mechanism of Schistosomicidal Action of Antimalarial Quinoline Methanols

Heme is an essential molecule to most living organisms, but once in a free state it exerts toxic effects. Blood-feeding organisms evolved efficient ways to detoxify free heme derived from hemoglobin digestion. A key mechanism present in some hematophagous organisms consists of the crystallization of heme into a pigment named hemozoin. Schistosoma mansoni is one of the etiologic agents of human schistosomiasis, a parasitic disease that affects over 200 million people in tropical and subtropical areas. Hemozoin formation represents the main heme detoxification pathway in S. mansoni. Here, we report that the antimalarial quinoline methanols quinine and quinidine exert schistosomicidal effects notably due to their capacity to interfere with hemozoin formation. When quinine or quinidine were administered intraperitoneally during seven days to S. mansoni-infected mice (75 mg/kg/day), both worm and eggs burden were significantly reduced. Interestingly, hemozoin content in female worms was drastically affected after treatment with either compound. We also found that quinine caused important changes in the cellular organization of worm gastrodermis and increased expression of genes related to musculature, protein synthesis and repair mechanisms. Together, our results indicate that interference with hemozoin formation is a valid chemotherapeutic target for development of new schistosomicidal agents

In vitro influence of photodynamic antimicrobial chemotherapy on staphylococcus aureus by using phenothiazines derivatives associated with laser/LED Light

ABSTRACT The aim of this study was to evaluate the effect of photodynamic antimicrobial chemotherapy (PACT) using phenothiazinium dyes -PTZ irradiated with red laser (ʎ660nm) or red-orange LED (ʎ632±2nm) on Staphylococcus aureus in vitro. triplicate tests were performed in 10 groups: control, Laser (L1 + P -and L2 + P -) bacterial suspensions were irradiated only with laser energy 2.4 and 4.8 J/cm 2 respectively, (Led1 + P -and Led2 + P -) irradiated only with LED energy 2.4 and 4.8 J/cm 2 respectively, (L1 + P + and L2 + P + ) irradiated with laser in the presence of 1μg/ml of photosensitizer, (Led1 + P + and Led2 + P + ) irradiated with LED in the presence of 1μg/ml of photosensitizer and finally (L -P + ) only in the presence of PTZ dye. Bactericidal effect of the PACT was assessed by counting colony-forming units. The results showed no significant difference on regards different energy densities on group PACT for both lights. PACT groups (L2 + P + and Led2 + P + ) compared to the Control showed significant reduction of CFUs. LED/Laser groups (L2 + P -and Led2 + P -) compared to control and PTZ groups showed also significant differences as groups LED/Laser (4.8J/cm 2 ) increased the average of CFUs. Although the results of this study have shown a reduction in average number of colonyforming units by the appropriate Laser or LED-dye treatment combination, it this topic requires further investigation

Blood-Feeding Induces Reversible Functional Changes in Flight Muscle Mitochondria of Aedes aegypti Mosquito

Background: Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energytransducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito Aedes aegypti, a vector of dengue and yellow fever. Methodology/Principal Findings: Blood-feeding caused a reversible reduction in mitochondrial oxygen consumption, an event that was parallel to blood digestion. These changes were most intense at 24 h after blood meal (ABM), the peak of blood digestion, when oxygen consumption was inhibited by 68%. Cytochromes c and a+a3 levels and cytochrome c oxidase activity of the electron transport chain were all reduced at 24 h ABM. Ultrastructural and molecular analyses of FM revealed that mitochondria fuse upon blood meal, a condition related to reduced ROS generation. Consistently, BF induced a reversible decrease in mitochondrial H2O2 formation during blood digestion, reaching their lowest values at 24 h ABM where a reduction of 51% was observed. Conclusion: Blood-feeding triggers functional and structural changes in hematophagous insect mitochondria, which may represent an important adaptation to blood feedin

Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative "Éminences Grises"?

This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term "cohabitant" is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together