RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection

Objective: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccinedemonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies. Setting: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. Participants: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. Outcome: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. Results: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at studymonth 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p 1/4 0.035, p 1/4 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p 1/4 0.478). Conclusions: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

Monitoring of malaria parasite resistance to chloroquine and sulphadoxine-pyrimethamine in the Solomon Islands by DNA microarray technology.

BACKGROUND: Little information is available on resistance to anti-malarial drugs in the Solomon Islands (SI). The analysis of single nucleotide polymorphisms (SNPs) in drug resistance associated parasite genes is a potential alternative to classical time- and resource-consuming in vivo studies to monitor drug resistance. Mutations in pfmdr1 and pfcrt were shown to indicate chloroquine (CQ) resistance, mutations in pfdhfr and pfdhps indicate sulphadoxine-pyrimethamine (SP) resistance, and mutations in pfATPase6 indicate resistance to artemisinin derivatives. METHODS: The relationship between the rate of treatment failure among 25 symptomatic Plasmodium falciparum-infected patients presenting at the clinic and the pattern of resistance-associated SNPs in P. falciparum infecting 76 asymptomatic individuals from the surrounding population was investigated. The study was conducted in the SI in 2004. Patients presenting at a local clinic with microscopically confirmed P. falciparum malaria were recruited and treated with CQ+SP. Rates of treatment failure were estimated during a 28-day follow-up period. In parallel, a DNA microarray technology was used to analyse mutations associated with CQ, SP, and artemisinin derivative resistance among samples from the asymptomatic community. Mutation and haplotype frequencies were determined, as well as the multiplicity of infection. RESULTS: The in vivo study showed an efficacy of 88% for CQ+SP to treat P. falciparum infections. DNA microarray analyses indicated a low diversity in the parasite population with one major haplotype present in 98.7% of the cases. It was composed of fixed mutations at position 86 in pfmdr1, positions 72, 75, 76, 220, 326 and 356 in pfcrt, and positions 59 and 108 in pfdhfr. No mutation was observed in pfdhps or in pfATPase6. The mean multiplicity of infection was 1.39. CONCLUSION: This work provides the first insight into drug resistance markers of P. falciparum in the SI. The obtained results indicated the presence of a very homogenous P. falciparum population circulating in the community. Although CQ+SP could still clear most infections, seven fixed mutations associated with CQ resistance and two fixed mutations related to SP resistance were observed. Whether the absence of mutations in pfATPase6 indicates the efficacy of artemisinin derivatives remains to be proven.

Comparative Genomics Suggests that the Fungal Pathogen Pneumocystis Is an Obligate Parasite Scavenging Amino Acids from Its Host's Lungs.

Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised patients. Progress in understanding its pathogenicity and epidemiology has been hampered by the lack of a long-term in vitro culture method. Obligate parasitism of this pathogen has been suggested on the basis of various features but remains controversial. We analysed the 7.0 Mb draft genome sequence of the closely related species Pneumocystis carinii infecting rats, which is a well established experimental model of the disease. We predicted 8'085 (redundant) peptides and 14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the closely related yeast Schizosaccharomyces pombe was used as a control for the annotation procedure (4'974 genes, 14.1% mapped). About two thirds of the mapped peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial enzymes for the basal metabolism and standard cellular processes. However, the proportion of P. carinii genes relative to those of S. pombe was significantly smaller for the "amino acid metabolism" category of pathways than for all other categories taken together (40 versus 114 against 278 versus 427, P<0.002). Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427, P<0.0001). This finding strongly suggests that species of the genus Pneumocystis are scavenging amino acids from their host's lung environment. Consequently, they would have no form able to live independently from another organism, and these parasites would be obligate in addition to being opportunistic. These findings have implications for the management of patients susceptible to P. jirovecii infection given that the only source of infection would be other humans.

A comparison of the energy budgets of two freshwater Pulmonates: Lymnaea peregra (Müller) and Physa acuta (Drap.)

The energy budgets of two freshwater gastropds, Lymnae peregra and Physa acuta, were compared in similar experimental conditions (20ºC, fed ad libitum with 24h-decayed lettuce), and found to differ in several ways. 1) L. Peregra has a higher assimilation efficiency than P. acuta (72% vs 60%). 2) These species assimilate different components of the ingested food: P. acuta uses a smaller, but more energetic part (probably mainly bacteria), whereas L. peregra assimilate a larger, but less energetic part (probably mainly cellulose). 3) L. peregra allocates more of its assimilated energy to oxygene consumption and mucus production (maintenance investments), wheras P. acuta invest more in growth and reproduction (production investments). Such differences are relevant to the natural habitat of these two species: P. acuta colonizes warm, eutrophic and temporary pools, where decaying material constitue the main part of available resources, and where adult mortality is high and impredictible. By contrast, L. peregra is frequently found in colder, oligotrophic and predictible environements, where living primary producers constitute the main part of available resources, and where biotic interactions are important factors of mortality.

Geochemical study of vertebrate fossils from the Upper Cretaceous (Santonian) Csehbanya Formation (Hungary): Evidence for a freshwater habitat of mosasaurs and pycnodont fish

The diverse vertebrate remains from the Upper Cretaceous freshwater settings at Iharkut, Hungary, contain two fossil groups, Pycnodontiformes fish and Mosasauridae that are almost exclusively known from marine palaeo-environments. Hence, their appearance in alluvial sediments is very unusual. Trace element and isotope compositions of the remains have been analyzed to investigate the taphonomy and the ecological differences among the different fossil groups present at Iharkut. All examined fossils have undergone post-depositional diagenetic alteration, which resulted in high concentrations of REE, U, and Fe, together with almost complete homogenization of delta(18)O(CO3) values. Similar REE patterns in different fossils suggest a common origin for all remains, hence the discovered species most likely lived in the same local ecosystem. Despite partial diagenetic overprinting, the delta(18)O(PO4) values of the fossils indicate sufficient taxon-specific isotopic diversity to permit some broad conclusions on the palaeo-environment of the fossils. In particular, it is apparent that the isotopic composition of the Pycnodontiformes fish and Mosasauridae remains is most compatible with a freshwater palaeo-habitat and incompatible with a marine palaeo-environment. In addition, the Sr concentration and isotope data indicate that the Pycnodontiformes and Mosasauridae likely lived predominantly in a freshwater environment and were not simply occasional visitors to the Iharkut river ecosystem. Regarding other fossil groups, high delta(18)O(PO4) values of Alligatoroidea and Iharkutosuchus teeth suggest that these small crocodile species might have inhabited swamps and ponds where the water was relatively rich in (18)O due to evaporation. (c) 2009 Elsevier B.V. All rights reserved.

Spermiogenesis and spermatozoon ultrastructure of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost fish Merluccius merluccius (Gadiformes: Merlucciidae)

Spermiogenesis and the ultrastructure of the spermatozoon of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost fish Merluccius merluccius (Linnaeus, 1758), have been studied by means of transmission electron microscopy. Spermiogenesis involves firstly the formation of a differentiation zone. It is characterized by the presence of two centrioles associated with striated rootlets, an intercentriolar body and an electron-dense material in the apical region of this zone. Later, two flagella develop from the centrioles, growing orthogonally in relation to the median cytoplasmic process. Flagella then undergo a rotation of 90° until they become parallel to the median cytoplasmic process, followed by the proximodistal fusion of the flagella with the median cytoplasmic process. The nucleus elongates and afterwards it migrates along the spermatid body. Spermiogenesis finishes with the appearance of the apical cone surrounded by the single helical crested body at the base of the spermatid. Finally, the narrowing of the ring of arched membranes detaches the fully formed spermatozoon. The mature spermatozoon of C. crassiceps is filiform and contains two axonemes of the 9 + '1' trepaxonematan pattern, a parallel nucleus, parallel cortical microtubules, and electron-dense granules of glycogen. The anterior extremity of the gamete exhibits a short electron-dense apical cone and one crested body, which turns once around the sperm cell. The first axoneme is surrounded by a ring of thick cortical microtubules that persist until the appearance of the second axoneme. Later, these thick cortical microtubules disappear and thus, the mature spermatozoon exhibits two bundles of thin cortical microtubules. The posterior extremity of the male gamete presents only the nucleus. Results are discussed and compared particularly with the available ultrastructural data on the former 'pseudophyllideans'. Two differences can be established between spermatozoa of Bothriocephalidea and Diphyllobothriidea, the type of spermatozoon (II vs I) and the presence/absence of the ring of cortical microtubules.

High quantitative and no molecular differentiation of a freshwater snail (Galba truncatula) between temporary and permanent water habitats.

We investigate the variation in quantitative and molecular traits in the freshwater snail Galba truncatula, from permanent and temporary water habitats. Using a common garden experiment, we measured 20 quantitative traits and molecular variation using seven microsatellites in 17 populations belonging to these two habitats. We estimated trait means in each habitat. We also estimated the distributions of overall genetic quantitative variation (QST), and of molecular variation (FST), within and between habitats. Overall, we observed a lack of association between molecular and quantitative variance. Among habitats, we found QST>FST, an indication of selection for different optima. Individuals from temporary water habitat matured older, at a larger size and were less fecund than individuals from permanent water habitat. We discuss these findings in the light of several theories for life-history traits evolution.

Sporozoite-mediated hepatocyte wounding limits Plasmodium parasite development via MyD88-mediated NF-kappa B activation and inducible NO synthase expression

Plasmodium sporozoites traverse several host cells before infecting hepatocytes. In the process, the plasma membranes of the cells are ruptured, resulting in the release of cytosolic factors into the microenvironment. This released endogenous material is highly stimulatory/immunogenic and can serve as a danger signal initiating distinct responses in various cells. Thus, our study aimed at characterizing the effect of cell material leakage during Plasmodium infection on cultured mouse primary hepatocytes and HepG2 cells. We observed that wounded cell-derived cytosolic factors activate NF-kappaB, a main regulator of host inflammatory responses, in cells bordering wounded cells, which are potential host cells for final parasite infection. This activation of NF-kappaB occurred shortly after infection and led to a reduction of infection load in a time-dependent manner in vitro and in vivo, an effect that could be reverted by addition of the specific NF-kappaB inhibitor BAY11-7082. Furthermore, no NF-kappaB activation was observed when Spect(-/-) parasites, which are devoid of hepatocyte traversing properties, were used. We provide further evidence that NF-kappaB activation causes the induction of inducible NO synthase expression in hepatocytes, and this is, in turn, responsible for a decrease in Plasmodium-infected hepatocytes. Furthermore, primary hepatocytes from MyD88(-/-) mice showed no NF-kappaB activation and inducible NO synthase expression upon infection, suggesting a role of the Toll/IL-1 receptor family members in sensing cytosolic factors. Indeed, lack of MyD88 significantly increased infection in vitro and in vivo. Thus, host cell wounding due to parasite migration induces inflammation which limits the extent of parasite infection

Ultrastructure of vitellogenesis and vitellocytes in the trypanorhynch cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax

This is the first TEM examination of vitellogenesis in the cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax and a member of a little-studied trypanorhynch family, the Aporhynchidae. The synthetic activity of vitellocytes plays two important functions in the developmental biology of cestodes: (1) their shell-globules serve in eggshell formation; and (2) their accumulated reserves of glycogen and lipids represent a food source for the developing embryo. In A. menezesi, vitelline follicles consist of cells at various stages of development, from peripheral, immature cells of the gonial type to mature cells towards the centre of the follicle. These stages are: (I) immature; (II) early differentiation; (III) advanced maturation; and (IV) mature. Gradual changes involved in this process occur within each stage. Vitellogenesis involves: (1) an increase in cell volume; (2) the development of a smooth endoplasmic reticulum and an accelerated formation and accumulation of both unsaturated and saturated lipid droplets, along with their continuous enlargement and fusion; (3) the formation of individual β-glycogen particles and their accumulation in the form of glycogen islands scattered among lipid droplets in the cytoplasm of maturing and mature vitellocytes; (4) the rapid accumulation of large, moderately saturated lipid droplets accompanied by dense accumulations of β-glycogen along with proteinaceous shell-globules or shell-globule clusters in the peripheral layer during the advanced stage of maturation; (5) the development of cisternae of granular endoplasmic reticulum that produce dense, proteinaceous shell-globules; (6) the development of Golgi complexes engaged in the packaging of this material; and (7) the progressive and continuous enlargement of shell-globules into very large clusters in the peripheral layer during the advanced stage of maturation. Vitellogenesis in A. menezesi, only to some extent, resembles that previously described for four other trypanorhynchs. It differs in: (i) the reversed order of secretory activities in the differentiating vitellocytes, namely the accumulation of large lipid droplets accompanied by glycogenesis or β-glycogen formation during early differentiation (stage II), i.e. before the secretory activity, which is predominantly protein synthesis for shell-globule formation (stage III); (ii) the very heavy accumulation of large lipid droplets during the final stage of cytodifferentiation (stage IV); and (iii) the small number of β-glycogen particles present in mature vitellocytes. Ultracytochemical staining with PA-TCH-SP for glycogen proved positive for a small number of β-glycogen particles in differentiating and mature vitellocytes. Hypotheses, concerning the interrelationships of patterns of vitellogenesis, possible modes of egg formation, embryonic development and life-cycles, are commented upon.

Ultrastructure of vitellogenesis and vitellocytes in the trypanorhynch cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax

This is the first TEM examination of vitellogenesis in the cestode Aporhynchus menezesi, a parasite of the velvet belly lanternshark Etmopterus spinax and a member of a little-studied trypanorhynch family, the Aporhynchidae. The synthetic activity of vitellocytes plays two important functions in the developmental biology of cestodes: (1) their shell-globules serve in eggshell formation; and (2) their accumulated reserves of glycogen and lipids represent a food source for the developing embryo. In A. menezesi, vitelline follicles consist of cells at various stages of development, from peripheral, immature cells of the gonial type to mature cells towards the centre of the follicle. These stages are: (I) immature; (II) early differentiation; (III) advanced maturation; and (IV) mature. Gradual changes involved in this process occur within each stage. Vitellogenesis involves: (1) an increase in cell volume; (2) the development of a smooth endoplasmic reticulum and an accelerated formation and accumulation of both unsaturated and saturated lipid droplets, along with their continuous enlargement and fusion; (3) the formation of individual β-glycogen particles and their accumulation in the form of glycogen islands scattered among lipid droplets in the cytoplasm of maturing and mature vitellocytes; (4) the rapid accumulation of large, moderately saturated lipid droplets accompanied by dense accumulations of β-glycogen along with proteinaceous shell-globules or shell-globule clusters in the peripheral layer during the advanced stage of maturation; (5) the development of cisternae of granular endoplasmic reticulum that produce dense, proteinaceous shell-globules; (6) the development of Golgi complexes engaged in the packaging of this material; and (7) the progressive and continuous enlargement of shell-globules into very large clusters in the peripheral layer during the advanced stage of maturation. Vitellogenesis in A. menezesi, only to some extent, resembles that previously described for four other trypanorhynchs. It differs in: (i) the reversed order of secretory activities in the differentiating vitellocytes, namely the accumulation of large lipid droplets accompanied by glycogenesis or β-glycogen formation during early differentiation (stage II), i.e. before the secretory activity, which is predominantly protein synthesis for shell-globule formation (stage III); (ii) the very heavy accumulation of large lipid droplets during the final stage of cytodifferentiation (stage IV); and (iii) the small number of β-glycogen particles present in mature vitellocytes. Ultracytochemical staining with PA-TCH-SP for glycogen proved positive for a small number of β-glycogen particles in differentiating and mature vitellocytes. Hypotheses, concerning the interrelationships of patterns of vitellogenesis, possible modes of egg formation, embryonic development and life-cycles, are commented upon.

Toxicity of triclosan, penconazole and metalaxyl on Caulobacter crescentus and a freshwater microbial community as assessed by flow cytometry.

Biocides are widely used for domestic hygiene, agricultural and industrial applications. Their widespread use has resulted in their introduction into the environment and raised concerns about potential deleterious effects on aquatic ecosystems. In this study, the toxicity of the biocides triclosan, penconazole and metalaxyl were evaluated with the freshwater bacterium Caulobacter crescentus and with a freshwater microbial community using a combination of single- and double-stain flow cytometric assays. Growth of C.  crescentus and the freshwater community were repressed by triclosan but not by penconazole or metalaxyl at concentrations up to 250 μM. The repressive effect of triclosan was dependent on culture conditions. Caulobacter crescentus was more sensitive to triclosan when grown with high glucose at high cell density than when grown directly in sterilized lake water at low cell density. This suggests that the use of conventional growth conditions may overestimate biocide toxicity. Additional experiments showed that the freshwater community was more sensitive to triclosan than C.  crescentus, with 10 nM of triclosan being sufficient to repress growth and change the phylogenetic composition of the community. These results demonstrate that isolate-based assays may underestimate biocide toxicity and highlight the importance of assessing toxicity directly on natural microbial communities. Because 10 nM of triclosan is within the range of concentrations observed in freshwater systems, these results also raise concerns about the risk of introducing triclosan into the environment.

Chemical composition and fatty acid contents in farmed freshwater prawns

The objective of this work was to evaluate the chemical composition and fatty acid contents of Amazonian and giant river prawns. After four-month farming, with the same diet for both species, palmitic and stearic acids were the main saturated fatty acids. Oleic acid was the main monounsatured fatty acid, and the eicosapentaenoic and docosahexaenoic acids were the most abundant polyunsaturated acids. Amazonian prawn has higher levels of protein and polyunsaturated fatty acids than those of the giant river prawn, which shows its potential for aquaculture.

Evolutionary aspects of population structure for molecular and quantitative traits in the freshwater snail Radix balthica.

Detecting the action of selection in natural populations can be achieved using the QST-FST comparison that relies on the estimation of FST with neutral markers, and QST using quantitative traits potentially under selection. QST higher than FST suggests the action of directional selection and thus potential local adaptation. In this article, we apply the QST-FST comparison to four populations of the hermaphroditic freshwater snail Radix balthica located in a floodplain habitat. In contrast to most studies published so far, we did not detect evidence of directional selection for local optima for any of the traits we measured: QST calculated using three different methods was never higher than FST. A strong inbreeding depression was also detected, indicating that outcrossing is probably predominant over selfing in the studied populations. Our results suggest that in this floodplain habitat, local adaptation of R. balthica populations may be hindered by genetic drift, and possibly altered by uneven gene flow linked to flood frequency.

Linking genetic and species diversities in a community of freshwater gastropods

Summary Biodiversity is usually studied through species or genetic diversities. To date, these two levels of diversity have remained the independent .fields of investigations of community ecologists and population geneticists. However, recent joint analyses of species and genetic diversities have suggested that common processes may underlie the two levels. Positive correlations between species diversity and genetic diversity may arise when the effects of drift and migration overwhelm selective effects. The first goal of this thesis was to make a joint investigation of the patterns of species and genetic diversity in a community of freshwater gastropods living in a floodplain habitat. The second goal was to determine, as far as possible, the relative influences of the processes underlying the patterns observed at each level. In chapter 2 we investigate the relative influences of different evolutionary forces in shaping the genetic structure of Radix balthica populations. Results revealed that the structure inferred using quantitative traits was lower or equal to the one inferred using neutral molecular markers. Consequently, the pattern of structure observed could be only due to random drift, possibly to uniform selection, but definitely not to selection for local optima. In chapter 3, we analyze the temporal variation of species and genetic diversities in five localities. An extended period of drought occurred at the end of the study period leading to decay of both species and genetic diversities. This parallel loss of diversity following a natural perturbation highlighted the role sometimes predominant of random drift over selection on patterns of biodiversity in a floodplain habitat. In chapter 4, we compare the spatial genetic structures of two sympatric species: Radix balthica and Planorbis carinatus. We found that R. balthica populations are weakly structured and have moderate to high values of gene diversity. In contrast, P. carinatus populations are highly structured and poorly diverse. Then we measured correlations between various indices of species and genetic diversity using genetic data .from the two species. We found only one significant correlation: between species richness and gene diversity of P. carinatus. This result highlights the .need to use genetic date from more than one species to infer correlations between species and genetic diversities. Overall, this thesis provided new insights into the common processes underlying patterns of species and genetic diversity. Résumé La biodiversité est généralement étudiée au niveau de la diversité génétique ou spécifique. Ces deux niveaux sont restés jusqu'à maintenant les domaines d'investigation séparés des généticiens des populations et des écologistes des communautés. Cependant, des analyses conjointes des diversités génétique et spécifique ont récemment suggéré que des processus similaires pouvaient influencer ces deux niveaux. Des corrélations positives entre les diversités génétique et spécifique pourraient être dues aux effets de migration et de dérive qui dominent les effets sélectifs. Le premier but de cette thèse était de faire une étude conjointe des diversités génétique et spécifique dans une communauté de gastéropodes d'eau douce. Le second objectif était de déterminer les influences relatives des différents processus liés à chaque niveau de diversité. Dans le chapitre 2 nous cherchons à déterminer quelles forces évolutives influencent la structure génétique de quatre populations de Radix balthica. La structure mesurée sur des traits quantitatifs s'est révélée être plus faible ou égale à celle mesurée avec des marqueurs moléculaires neutres. La structure observée pourrait ainsi être due uniquement à la dérive génétique, potentiellement à la sélection uniforme, mais en aucun cas à la sélection locale pour différents optima. Dans le chapitre 3 nous analysons la variation temporelle des diversités génétique et spécifique dans cinq localités. Une récente période de sécheresse a causé une diminution parallèle des deux niveaux de diversité. Cette perturbation à mis en évidence le rôle parfois prépondérant de la dérive par rapport à celui de la sélection dans le déterminisme de la biodiversité dans un écosytème alluvial. Dans le chapitre 4, nous comparons la structure génétique spatiale de deux espèces vivant en sympatrie : Radix balthica et Planorbis carinatus. Les populations de R. balthica sont peu structurées et présentent un niveau de diversité relativement élevé alors que celles de P. carinatus sont fortement structurées et peu diversifiées. Nous avons ensuite mesuré différentes corrélations entre les diversités génétique et spécifique, mais la seule relation significative a été trouvée entre la richesse spécifique et la diversité génétique de P. carinatus. Ainsi, cette thèse a permis de découvrir de nouveaux aspects des processus qui influencent en parallèle la diversité aux niveaux génétique et spécifique.

Are protozoan metacaspases potential parasite killers?

Mechanisms concerning life or death decisions in protozoan parasites are still imperfectly understood. Comparison with higher eukaryotes has led to the hypothesis that caspase-like enzymes could be involved in death pathways. This hypothesis was reinforced by the description of caspase-related sequences in the genome of several parasites, including Plasmodium, Trypanosoma and Leishmania. Although several teams are working to decipher the exact role of metacaspases in protozoan parasites, partial, conflicting or negative results have been obtained with respect to the relationship between protozoan metacaspases and cell death. The aim of this paper is to review current knowledge of protozoan parasite metacaspases within a drug targeting perspective.