The Plasmodium falciparum protein PfMRP1 functions as an influx ABC transporter

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play an important role in mediating solute or drug transport across cellular membranes. Although this class of transporters has been well characterized in diverse organisms little is known about the physiological roles in Plasmodium falciparum, the deadliest malaria parasite species. We studied the Plasmodium falciparum Multidrug Resistance-associated Protein 1 (PfMRP1; PF3D7_0112200), an ABC transporter localized to the parasite plasma membrane, generating genetic disrupted parasites. We demonstrate that parasites with disrupted pfmrp1 are resistant to folate analogs, methotrexate and aminopterin, with antimalarial activity. This phenotype occurs due to reduction in compound accumulation in the parasite cytoplasm. Phylogenetic analysis supports pfmrp1 being distantly related to ABC transporters in other eukaryotes, suggesting an unusual function. We propose that PfMRP1 can act as a solute importer, a function not previously observed in this organism.

Contribution of Transcriptome to Elucidate the Biology of Plasmodium spp

In the present review, we discuss some of the new technologies that have been applied to elucidate how Plasmodium spp escape from the immune system and subvert the host physiology to orchestrate the regulation of its biological pathways. Our manuscript describes how techniques such as microarray approaches, RNA-Seq and single-cell RNA sequencing have contributed to the discovery of transcripts and changed the concept of gene expression regulation in closely related malaria parasite species. Moreover, the text highlights the contributions of high-throughput RNA sequencing for the current knowledge of malaria parasite biology, physiology, vaccine target and the revelation of new players in parasite signaling.

Avian haemosporidian parasites of accipitriform raptors

Background The order Accipitriformes comprises the largest group of birds of prey with 260 species in four families. So far, 21 haemosporidian parasite species have been described from or reported to occur in accipitriform birds. Only five of these parasite species have been characterized molecular genetically. The first part of this study involved molecular genetic screening of accipitriform raptors from Austria and Bosnia-Herzegovina and the first chromogenic in situ hybridization approach targeting parasites in this host group. The aim of the second part of this study was to summarize the CytB sequence data of haemosporidian parasites from accipitriform raptors and to visualize the geographic and host distribution of the lineages. Methods Blood and tissue samples of 183 accipitriform raptors from Austria and Bosnia-Herzegovina were screened for Plasmodium, Haemoproteus and Leucocytozoon parasites by nested PCR, and tissue samples of 23 PCR-positive birds were subjected to chromogenic in situ hybridization using genus-specific probes targeting the parasites’ 18S rRNAs. All published CytB sequence data from accipitriform raptors were analysed, phylogenetic trees were calculated, and DNA haplotype network analyses were performed with sequences from clades featuring multiple lineages detected in this host group. Results Of the 183 raptors from Austria and Bosnia-Herzegovina screened by PCR and sequencing, 80 individuals (44%) were infected with haemosporidian parasites. Among the 39 CytB lineages detected, 18 were found for the first time in the present study. The chromogenic in situ hybridization revealed exo-erythrocytic tissue stages of Leucocytozoon parasites belonging to the Leucocytozoon toddi species group in the kidneys of 14 infected birds. The total number of CytB lineages recorded in accipitriform birds worldwide was 57 for Leucocytozoon, 25 for Plasmodium, and 21 for Haemoproteus. Conclusion The analysis of the DNA haplotype networks allowed identifying numerous distinct groups of lineages, which have not yet been linked to morphospecies, and many of them likely belong to yet undescribed parasite species. Tissue stages of Leucocytozoon parasites developing in accipitriform raptors were discovered and described. The majority of Leucocytozoon and Haemoproteus lineages are specific to this host group, but most Plasmodium lineages were found in birds of other orders. This might indicate local transmission from birds kept at the same facilities (raptor rescue centres and zoos), likely resulting in abortive infections. To clarify the taxonomic and systematic problems, combined morphological and molecular genetic analyses on a wider range of accipitriform host species are needed.

An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India

Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions.

Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets

The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct adaptations to the differences in nutritional availabilities, either relying on biosynthetic pathways or by salvaging metabolites from their host. Pantothenate (Pan, vitamin B5) is the precursor for the synthesis of an essential cofactor, coenzyme A (CoA), but among the apicomplexans, only the coccidian subgroup has the ability to synthesize Pan. While the pathway to synthesize CoA from Pan is largely conserved across all branches of life, there are differences in the redundancy of enzymes and possible alternative pathways to generate CoA from Pan. Impeding the scavenge of Pan and synthesis of Pan and CoA have been long recognized as potential targets for antimicrobial drug development, but in order to fully exploit these critical pathways, it is important to understand such differences. Recently, a potent class of pantothenamides (PanAms), Pan analogs, which target CoA-utilizing enzymes, has entered antimalarial preclinical development. The potential of PanAms to target multiple downstream pathways make them a promising compound class as broad antiparasitic drugs against other apicomplexans. In this review, we summarize the recent advances in understanding the Pan and CoA biosynthesis pathways, and the suitability of these pathways as drug targets in Apicomplexa, with a particular focus on the cyst-forming coccidian, Toxoplasma gondii, and the haemosporidian, Plasmodium falciparum.

Паразиты рыб горных озер бассейна Верхней Колымы. 1. Озера большой и малый Дарпир.

The first data on the parasite fauna of fish from the mountain lakes Bolshoy and Maly Darpir at the southern spurs of the Chersky Ridge (Momsky District, Yakutia) are presented. 7 species of fish have been studied, in which 34 species of parasites have been found: 33 species of helminths and 1 species of parasitic copepods, belonging to 22 genera, 16 families, 12 orders, 7 classes of 4 types of the animal kingdom. Trematodes completely dominate by the number of species among helminths (16 species); cestodes are half as many (8 species); these are followed by nematodes and spiny-headed worms (5 and 4 species, respectively). The greatest variety of parasites was found in the East Siberian grayling (22 species) and the Arctic char (19 species). Next to the latter in terms of the number of parasite species, there went the Kolyma sculpin (13 species), round whitefish (10 species each), sucker (9 species), eelpout, and common minnow (7 species each). Only one parasite species, the Neoechinorhynchus salmonis Ching, 1984 spiny-headed worm, is common for all studied fish. The second species of spiny-headed worms, Pseudoechinorhynchus borealis (Linstow, 1901), not found only in the round whitefish, was first recorded in fish of the Okhotsk-Kolyma area and in the sucker as a new definitive host.

Synthesis of novel aminoquinolines with potential leishmanicidal and antimalarial biological activity / Síntese de novas aminoquinolinas com potencial actividade biológica leishmanicida e antimalárica

Leishmaniasis is a disease transmitted by different parasite species of the genus Leishmania, while malaria, by protozoa of the genus Plasmodium sp. These diseases affect tropical and subtropical regions, where about half of the world's population live. However, leishmaniasis and malaria are considered neglected diseases because these regions are poor, and consequently have precarious essential sanitation networks. In response to the lack of vaccines and effective medical measures, some natural and synthetic medicines are used as forms of treatment, such as quinoline derivatives necessary to treat malaria. Even so, the parasites have shown resistance to forms of treatment, which makes needed the constant development of new drugs with potential against them. Quinoline derivatives, chloroquine analogues, have potential activity for the diseases of interest, while anilines are molecules used in nucleophilic reactions on different substrates. Therefore, the work consisted of exploring the synthesis between these two compounds through subsequent reactions involving the formation of intermediates that resulted in the products of interest. Twelve novel derivatives with potential leishmanicidal and antimalarial biological activity were synthesized. The molecules produced were purified and rightly characterized by several methods, such as mass spectrometry, infrared spectroscopy, and Nuclear Magnetic Resonance of Carbon (13C) and Hydrogen (1H). Also, were obtained the melting points of the synthesized molecules. Finally, all products were sent for biological tests against the parasites, getting highly effective results for the protozoa responsible for leishmaniasis.

Component Endoparasite Communities Mirror Life-History Specialization in Syntopic Reed Frogs (Hyperolius spp.)

Most of our knowledge on the processes structuring parasite communities in amphibians originate from temperate-zone taxa, whereas Afrotropical communities have been neglected so far. We found evidence that ecological fitting of the hosts and, probably, differential immune response may influence the variation in parasite species richness, prevalence, and infestation intensity of East African frogs Hyperolius kivuensis and H. viridiflavus. The most closely related host species share the same macrohabitat (that implies the same pool of potential parasites), but differ in microhabitat preference, so that a comparative analyses of syntopic and allopatric populations is expedient to reveal ecological fitting. We detected 11 parasite species (one annelid, four nematodes, five trematodes, one cestode) and two endocommensal species (protozoans). The component parasite communities included 4–5 helminth species in H. kivuensis and 6–8 in the more aquatic H. viridiflavus, supporting the hypothesis that trematode diversity increases with the amount of time spent in water. Five parasite species (Orneoascaris chrysanthemoides, Clinostomum chabaudi, an undetermined echinostomatid) and two protozoans (Nyctotheroides sp., and Protoopalina sp.) are shared among the syntopic amphibian populations. This finding indicates a similar susceptibility of these amphibians to infestation from the local parasite pool. Yet, the low prevalence of single- and multi-species infestations in H. kivuensis indicates that parasite clearing by its immune response is probably more effective and prominent than in H. viridiflavus. Therefore, H. viridiflavus suffered from significantly reduced short-term survival due to the infection. Thus, we conclude that the processes structuring component parasite communities in amphibians do not differ generally between temperate-zone and Afrotropical host species, but they do in the magnitude of ecological fitting.

Effects of Leishmania Species on Immune Response against Malaria Parasite in Malaria Leishmania Coinfections

Both malaria and leishmania are most widespread protozoon parasitic diseases, certainly in tropical countries of the world. Malaria leishmania coinfection is common in leishmaniasis endemic areas which is mostly endemic to malaria too. Researchers notice that in cases of malaria leishmania coinfection , leishmania species find the some extent the outcome of malaria infection , but also behavior of malaria parasite species play a significant role to figure the consequences of it. While L. donovani protect from severe malaria complications by suppression of major histocompatibility class Ⅱ , so it diminish the clinical severity of malaria but not malaria parasite density due to dysfunction of major histocompatibility class I, which controlled by suppressed one, In another side L. mexicana tends to sequester in macrophages and lead to severe clinical outcomes when it coexisted with malaria parasite at same host. Experimental studies required to know more information about coinfection of different malaria and leishmania species to establish clinical research. Leishmania infection excluded when studies aim to assess the immune response to only malaria parasite, experimental studies required involving different species of malaria and leishmania.

Assessment of Vitamin D Status in Patients Suffering from Uncomplicated Malaria in a Health Center in the District of Abidjan (Côte d’Ivoire)

Aims: The pathophysiology of Plasmodium falciparum infection is most often associated with anemia and immune deficiency. Given the important role of vitamin D in the synthesis of hemoglobin and in the stimulation of the immune system, it would be essential to assess the vitamin D status of patients with malaria in order to improve the quality of treatment management. Methodology: A thick drop and a blood smear were used to determine parasite density and parasite species respectively. The complete blood count was performed using an automated analyzer labelled Sysmex XN 1000i. Biochemical parameters such as calcium and phosphorus were determined using the Cobas C311 Hitachi. The Vidas was used to determine the concentrations of 25 (OH) -vitamin D. Results: The results showed a decrease in 25 (OH) -vitamin D concentrations in relation to the parasite density and anemia observed in patients with uncomplicated malaria. Conclusion: Vitamin D status in patients with uncomplicated malaria could represent an essential biomarker in the monitoring of antimalarial treatment.