Major Parasites Research Articles

DNA barcode identification of a tropical liver fluke (Fasciola gigantica) in cattle from Oyo, southwestern Nigeria

BackgroundFascioliasis is a major parasite illness that affects ruminants, both domesticated and free, and has an impact on public health and animals’ productivity. The genetic diversity of Fasciola species in cattle from Oyo, Oyo State, Nigeria is yet not well understood. In this study, the genetic diversity of Fasciola gigantica in slaughtered cattle in Oyo was examined using a molecular-based approach targeting the mitochondrial cytochrome C oxidase subunit I (COI) gene region.ResultsOne hundred flukes were gathered from slaughtered cattle, and their COI gene sequences were analyzed using maximum likelihood methods. The results of phylogenetic analysis showed genetic similarities between Nigerian F. gigantica and isolates from Algeria, Egypt, Iran, Sudan, China, Japan and Nigeria. The predominant DNA substitution was the A to T transversion, while the least common substitution was the G to A transition.ConclusionOur results show how useful the COI gene region is for examining intraspecific differences between F. gigantica isolates. The genetic similarity observed among the sampled F. gigantica populations suggests the value of mitochondrial DNA sequences as a marker for the accurate identification and characterization of Fasciola species across different ruminants.

Occurrence and molecular characterization of Giardia spp. in snakes from China

Giardia intestinalis is a major diarrhea-causing parasite that colonizes the proximal small intestine of humans and various other mammalian species, including pets and livestock. Despite its global occurrence, there is limited information about the epidemiology of Giardia in reptiles, particularly snakes. The aim of this study was to amplify the beta-giardin (bg) gene of Giardia by polymerase chain reaction (PCR), followed by a comparative evolutionary tree analysis to determine the occurrence and molecular characterization of Giardia in snakes. We collected 603 asymptomatic samples from 26 provinces in China, representing species such as Pantherophis guttatus, Pantherophis obsoletus, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getula, and Heterodon nasicus. Ultimately, a occurrence of Giardia infection of 4.15 % was detected in these snakes, with corn snakes (Pantherophis guttatus) having a significantly higher occurrence than other species. Molecular analysis identified assemblage F as the predominant genotype, and also identified an assemblage B that can infect humans and a variety of mammals. The results of this study illustrate the potential risk of transmission of Giardia from snakes to humans, especially in environments where close contact occurs. The present epidemiological study examines epidemiological investigations of Giardia in reptiles, provides data to understand the zoonotic risk of Giardia, and emphasizes the need for targeted surveillance, stringent hygiene measures, and public awareness campaigns to reduce these risks.

Population structure analysis of Phlebotomus papatasi populations using transcriptome microsatellites: possible implications for leishmaniasis control and vaccine development

BackgroundPhlebotomus papatasi is considered the primary vector of Leishmania major parasites that cause zoonotic cutaneous leishmaniasis (ZCL) in the Middle East and North Africa. Phlebotomus papatasi populations have been studied extensively, revealing the existence of different genetic populations and subpopulations over its large distribution range. Genetic diversity and population structure analysis using transcriptome microsatellite markers is important to uncover the vector distribution dynamics, essential for controlling ZCL in endemic areas.MethodsIn this study, we investigated the level of genetic variation using expressed sequence tag-derived simple sequence repeats (EST-SSRs) among field and colony P. papatasi samples collected from 25 different locations in 11 countries. A total of 302 P. papatasi sand fly individuals were analyzed, including at least 10 flies from each region.ResultsThe analysis revealed a high-level population structure expressed by five distinct populations A through E, with moderate genetic differentiation among all populations. These genetic differences in expressed genes may enable P. papatasi to adapt to different environmental conditions along its distribution range and likely affect dispersal.ConclusionsElucidating the population structuring of P. papatasi is essential to L. major containment efforts in endemic countries. Moreover, the level of genetic variation among these populations may improve our understanding of Leishmania–sand fly interactions and contribute to the efforts of vaccine development based on P. papatasi salivary proteins.Graphical

Trends and antibiotic susceptibility patterns of diarrhoeal pathogens - experience over 14 years in southern India.

Introduction. Enteric pathogens contribute significantly to morbidity in a developing country such as India. Early and prompt diagnosis of diarrhoeal diseases can reduce the mortality rate, particularly in children. The pattern of sensitivity to antimicrobials for the common pathogens can vary from time to time. The present study was conducted to study the pathogen distribution and antimicrobial susceptibility pattern during the study period (January 2010 to December 2023). Hypothesis/gap statement. Studying the changing trend in the antimicrobial sensitivity pattern of diarrhoeal pathogens over a decade can help to plan future treatment options. Aim. This study was undertaken to provide insights into the changing pattern of pathogen distribution and antimicrobial susceptibility for enteric pathogens over 14 years. Methods. A retrospective observational cohort analysis was conducted on all the stool pathogens isolated from the samples received in the microbiology department of a tertiary care hospital from 2010 to 2023. The demographic details, stool microscopy, culture reports, and antimicrobial susceptibility patterns were noted. Results. A total of 18 336 stool specimens were received in the microbiology laboratory between January 2010 and December 2023, of which 1354 specimens had diarrhoeal pathogens grown in culture. Out of these 1354 specimens, 591 (44%) had Salmonella, 471 (35%) Shigella, 181 (13%) Vibrio cholerae, and 80 (6%) Aeromonas species. Among these pathogens, susceptibility to ceftriaxone was seen in 93% (552 isolates) of Salmonella species, 89% (420 isolates) of Shigella species, and 95% (171 isolates) of Vibrio cholerae; 91% (73 isolates) of Aeromonas species were susceptible to chloramphenicol. Some major parasites were also observed on microscopy. Conclusion. Timely diagnosis of diarrhoeal pathogens can be life-saving for patients at the extremes of age, i.e. in children and the elderly. Pathogens can exhibit a changing susceptibility pattern to antibiotics, which should be regularly observed to plan future therapy.

Synthesis and in vitro evaluation shows disquaramide compounds are a promising class of anti-leishmanial drugs.

An increasing number of treatment failures with current pharmaceutics, as well as a lack of a vaccine, demonstrates the need to develop new treatment options for leishmaniasis. Herein, we describe the synthesis and in vitro analysis of 24 disquaramide compounds targeting the Leishmania major parasite. Of the compounds that were evaluated, six of them ( 13 , 19 , 20 , 22 , 24 , and 26 ) were capable of significantly decreasing the number of parasites by up to 42% compared to the control by day four. This demonstrates that disquaramides either impair parasite replication or have leishmancidal effects. Additionally, none of the disquaramide compounds tested displayed host cell cytotoxicity. These experiments provide evidence that disquaramides have the potential to be effective anti-leishmanial therapeutics.

The Immune Memory Response of In Vitro-Polarised Th1, Th2, and Th17 Cells in the Face of Ovalbumin-Transgenic Leishmania major in a Mouse Model.

Th1 and Th2 cytokines determine the outcome of Leishmania major infection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenic Leishmania major strains expressing membrane-associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) were used as a model to study whether fully differentiated Th1/Th2 and Th17 cells can recall immune memory and tolerate pathogen manipulation. Naïve OT-II T cells were polarised in vitro into Th1/Th2 cells, and these cells were transferred adoptively into recipient mice. Following the transferral of the memory cells, the recipient mice were challenged with OVA transgenic Leishmania major and a wild-type parasite was used a control. The in vitro-polarised T helper cells continued to produce the same cytokine signatures after being challenged by both forms of OVA-expressing Leishmania major parasites in vivo. This suggests that antigen-experienced cells remain the same or unaltered in the face of OVA-transgenic Leishmania major. Such ability of these antigen-experienced cells to remain resilient to manipulation by the parasite signifies that vaccines might be able to produce immune memory responses and defend against parasitic immune manipulation in order to protect the host from infection.

The Therapeutic Effect of Shirvan Herbal Ointment on Human Cutaneous Leishmaniasis Compared with Glucantime.

Cutaneous leishmaniasis (CL) infection is caused by the Leishmania major (L. major) parasite and affects 1.5 to 2 million people worldwide each year. Although research into vaccines and antiparasitic drugs has been somewhat successful, their adverse effects include high toxicity, prolonged regeneration, and scarring. This has highlighted the importance of research to replace natural products with antibacterial and antioxidant properties, such as vegetable extracts and oils. Since, the anti-leishmaniasis effect of each of the components of Shirvan herbal ointment (aloe vera, Brazembel, Nigella sativa, propolis, lavender, and olive oil) has been separately studied and confirmed, it seems that the combination of these components can have an increasing anti-leishmanial effect to treat CL. Therefore, this study investigated the therapeutic impact of Shirvan herbal ointment on Iranian patients with leishmaniasis in comparison with glucantime (meglumine). Sixty patients with leishmaniasis were divided into the control and test groups. The control and test groups received intralesional glucantime and Shirvan herbal cream (two times daily), respectively. The size mean of the lesion was 51.5 ± 32.5 before and 11.11 ± 16.28 after treatment in the control group and 50.8 ± 31.2 before and 0.0 ± 0.0 after treatment in the test group. In addition, the period mean of treatment was 43.9 ± 14.4 days and 30.5 ± 7.4 days in the control and test groups, respectively. There was a significant difference in lesion size between the two groups after treatment. Data suggested that Shirvan herbal ointment can be an alternative drug in the treatment of human CL.

Epidemiology and distribution of gastrointestinal parasites in fattening pig farms in northern Italy

In Italy, pig breeding is characterised by intensive farms in which parasitic diseases often present a subclinical pattern, while being responsible for decreased animal welfare and great economic losses. The present study aimed to assess the prevalence of major parasites in pigs, and, for this purpose, 880 faecal samples of fattening pigs raised in 22 intensive farms located in northern Italy were collected in two different sampling sessions, at the beginning and end of the fattening cycle. For the detection of helminth eggs and coccidian oocysts, a quantitative flotation technique was used, whereas a conventional PCR was performed to confirm the identification of cestode eggs found by copromicroscopic analysis. Moreover, data regarding herd management were collected to assess risk factors for parasite occurrence. A total of 95 samples were positive for at least one parasitic taxon (10.8%); the most detected parasite was Ascaris suum (7.6%), followed by Trichuris suis (1.7%) and Cystoisospora suis (0.9%). Further, eggs with morphometric features compatible with those of Hymenolepis diminuta were detected in 16 samples (1.8%), and the analysis of sequences confirmed the identification of cestode eggs. Statistical analysis showed that large farms and those applying the all-in/all-out system were associated with a lower risk of nematode infection. This study provided data on prevalence and burden of gastrointestinal parasites in two different times of the fattening cycle. It was evidenced that endoparasites are persistent, albeit with low prevalences, and would need specific measures to reduce their effects on both animal health and productivity.

Risk of invasion and disease transmission by the Australasian freshwater snail Orientogalba viridis (Lymnaeidae): a field and experimental study

BackgroundBiological invasions pose risks to the normal functioning of ecosystems by altering the structure and composition of several communities. Molluscs stand out as an extensively studied group given their long history of introduction by either natural or anthropogenic dispersal events. An alien population of the lymnaeid species Orientogalba viridis was first sighted in 2009 in southern Spain. In its native range (Australasian), this species is one of the main intermediate hosts of Fasciola hepatica, a major worldwide trematode parasite largely affecting humans, domestic animals and wildlife.MethodsWe collected field populations of O. viridis from its native (Malaysia) and invaded (Spain) ranges. We performed detailed morphoanatomical drawings of the species and screened for natural infection of parasites. Individuals were molecularly characterized using ITS2 for comparison with existing sequences in a fine phylogeography study. We founded experimental populations at two different conditions (tropical, 26 °C and temperate, 21 °C) to study the life-history traits of exposed and non-exposed individuals to different F. hepatica isolates.ResultsWe found a 9% natural prevalence of trematode infection (98% similarity with a sequence of Hypoderaeum conoideum [Echinostomatidae]) in the Spanish field population. The haplotypes of O. viridis found in our study from Spain clustered with Australian haplotypes. Experimental infection with F. hepatica was successful in both experimental conditions but higher in tropical (87% prevalence) than in temperate (73%). Overall lifespan, however, was higher in temperate conditions (mean 32.5 ± 7.4 weeks versus 23.3 ± 6.5) and survivorship remained above 70% during the first 20 weeks. In parasite-exposed populations, life expectancy dropped from an overall 37.75 weeks to 11.35 weeks but still doubled the time for initial cercariae shedding. Cercariae shedding started at day 23 post-exposure and peaked between days 53 and 67 with an average of 106 metacercariae per snail.ConclusionsWhether O. viridis will succeed in Europe is unknown, but the odds are for a scenario in which a major snail host of F. hepatica occupy all available habitats of potential transmission foci, ravelling the epidemiology of fasciolosis. This research provides a comprehensive understanding of O. viridis biology, interactions with parasites and potential implications for disease transmission dynamics, offering valuable insights for further research and surveillance.Graphical

Structure-Activity Study on Substituted, Core-Extended, and Dyad Naphthalene Diimide G-Quadruplex Ligands Leading to Potent Antitrypanosomal Agents.

Several G-quadruplex nucleic acid (G4s) ligands have been developed seeking target selectivity in the past decade. Naphthalene diimide (NDI)-based compounds are particularly promising due to their biological activity and red-fluorescence emission. Previously, we demonstrated the existence of G4s in the promoter region of parasite genomes, assessing the effectiveness of NDI-derivatives against them. Here, we explored the biological activity of a small library of G4-DNA ligands, exploiting the NDI pharmacophore, against both Trypanosoma brucei and Leishmania major parasites. Biophysical and biological assays were conducted. Among the various families analyzed, core-extended NDIs exhibited the most promising results concerning the selectivity and antiparasitic effects. NDI 16 emerged as the most potent, with an IC50 of 0.011 nM against T. brucei and remarkable selectivity vs MRC-5 cells (3454-fold). Fascinating, 16 is 480-fold more potent than the standard drug pentamidine (IC50 = 5.3 nM). Cellular uptake and parasite localization were verified by exploiting core-extended NDI red-fluorescent emission.

Genetic diversity of the PvMSP-3α gene in Plasmodium vivax isolates circulating in the National Capital Region (NCR) of India

Malaria is still a public health problem in tropical countries like India; major malaria parasite species are Plasmodium falciparum and P. vivax. Of which, P. vivax is responsible for ∼40% of the malaria burden at least in the Indian scenario. Unfortunately, there is limited data on the population structure and genetic diversity of P. vivax parasites in India. In this study, we investigated the genetic diversity of P. vivax strains in the South-west district, Delhi and, Nuh district, Haryana [National Capital Region (NCR)], using a polymorphic marker- P. vivax merozoite surface protein-3α (PvMSP-3α) gene. Dried blood spots from microscopically confirmed P. vivax patients were used for investigation of the PvMSP-3α gene. PCR-RFLP was performed on the PvMSP-3α gene to investigate the genotypes and allelic variability with HhaI and AluI restriction enzymes. In total, 40 successfully PCR amplified PvMSP-3α gene segments were subjected to RFLP analysis. Amplified products showed three different base pair size variations viz. genotype A in 31(77.5%), genotype B in 4(10%) and genotype C in 5(12.5%) P. vivax specimens. RFLP with HhaI and AluI revealed 17 (H1-H17) and 25 (A1-A25) allelic variants, respectively. Interestingly, two similar sub-allelic variants, ie. H8 (with HhaI), and A4 (with AluI) clustered within the rural area of Nuh district, Haryana in two samples. With this study, we propose to commission such type of genetic diversity analysis of P. vivax to investigate the circulating genotypes of the parasites from distinct geographical locations across India, that can have significant implications in understanding the population structures of P. vivax.

ScRNA-seq reveals transcriptional dynamics of Encephalitozoon intestinalis parasites in human macrophages.

Microsporidia are single-celled intracellular parasites that cause opportunistic diseases in humans. Encephalitozoon intestinalis is a prevalent human-infecting species that invades the small intestine. Dissemination to other organ systems is also observed, and is potentially facilitated by macrophages. The macrophage response to infection and the developmental trajectory of the parasite are not well studied. Here we use single cell RNA sequencing to investigate transcriptional changes in both the host and parasite during infection. While a small population of infected macrophages mount a response, most remain transcriptionally unchanged, suggesting that the majority of parasites may avoid host detection. The parasite transcriptome reveals large transcriptional changes throughout the life cycle, providing a blueprint for parasite development. The stealthy microsporidian lifestyle likely allows these parasites to harness macrophages for replication and dissemination. Together, our data provide insights into the host response in primary human macrophages and the E. intestinalis developmental program.

Designing Antitrypanosomal and Antileishmanial BODIPY Derivatives: A Computational and In Vitro Assessment.

Leishmaniasis and Human African trypanosomiasis pose significant public health threats in resource-limited regions, accentuated by the drawbacks of the current antiprotozoal treatments and the lack of approved vaccines. Considering the demand for novel therapeutic drugs, a series of BODIPY derivatives with several functionalizations at the meso, 2 and/or 6 positions of the core were synthesized and characterized. The in vitro activity against Trypanosoma brucei and Leishmania major parasites was carried out alongside a human healthy cell line (MRC-5) to establish selectivity indices (SIs). Notably, the meso-substituted BODIPY, with 1-dimethylaminonaphthalene (1b) and anthracene moiety (1c), were the most active against L. major, displaying IC50 = 4.84 and 5.41 μM, with a 16 and 18-fold selectivity over MRC-5 cells, respectively. In contrast, the mono-formylated analogues 2b and 2c exhibited the highest toxicity (IC50 = 2.84 and 6.17 μM, respectively) and selectivity (SI = 24 and 11, respectively) against T. brucei. Further insights on the activity of these compounds were gathered from molecular docking studies. The results suggest that these BODIPYs act as competitive inhibitors targeting the NADPH/NADP+ linkage site of the pteridine reductase (PR) enzyme. Additionally, these findings unveil a range of quasi-degenerate binding complexes formed between the PRs and the investigated BODIPY derivatives. These results suggest a potential correlation between the anti-parasitic activity and the presence of multiple configurations that block the same site of the enzyme.

Characterization of Escherichia coli Strains for Novel Production of Plasmodium ovale Lactate Dehydrogenase.

Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles Plasmodium vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. P. ovale receives relatively less attention compared to other major parasites, such as P. falciparum and P. vivax, primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three Escherichia coli strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for P. ovale LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics.

Molecular characterization of Lernathropus kroyeri from intensive aquaculture and pathophysiology of infested sea bass

The copepod Lernathropus kroyeri constitutes one of the major parasites for the Mediterranean aquaculture, infesting the sea bass Dicentrarchus labrax causing thus disruptions of growth performance and occasionally mortalities. Despite the large spread and the high frequency of this parasite in mariculture farms of Eastern Mediterranean, L. kroyeri genetic profile from aquaculture as well as the pathophysiological response of D. labrax have not been studied so far. Keeping this in mind, in the present study we investigated the L. kroyeri infestation on D. labrax from two farms in Greece, examining both healthy and heavy parasitized individuals. Assays included histopathology, phylogenetic reconstruction of the parasite and physiological response of the fish by the means of antioxidant, inflammatory metabolic and stress related gene expression analysis at both mRNA and protein levels. Genetic analysis indicated that L. kroyeri composes a monophyletic group, highly phylogenetically distant from other congeneric groups. Heavy infested D. labrax witnessed a significantly increased immune response that further led to oxidative stress and metabolic alterations. Overall, our results demonstrate the, seasonally independent, high infestation of this parasitic copepods, which continue to affect Mediterranean intensive aquaculture systems.

Retrospective study on occurrence of bovine gastrointestinal parasitic infections in different regions of Haryana

The production and reproduction of livestock is hampered by the presence of gastrointestinal (GI) parasitic infections. The effect of parasites ranges from anorexia, loss of body condition, anaemia, diarrhoea, protein losing enteropathy and loss of body condition apart from aforementioned direct and indirect effects on the animals leads to huge economic losses to livestock owners. In the present study, a total of 1669 faecal samples from cattle (n=550) and buffaloes (n=1119) with the history of diarrhoea or digestive disturbances were processed for presence of parasitic infections at different disease investigation laboratories (Ambala, Bhiwani, Mahendragarh and Rohtak) of Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana from July 2021 to June 2022. All the faecal samples were processed by floatation and sedimentation methods for detection of parasitic eggs and the results revealed that 29.6% cattle and 34.7% buffaloes were positive for GI parasites. Buxtonella sulcata (17.7%), Amphistomes (5.2%), and Strongyles (6.9%) were the major parasites observed in cattle and buffaloes. The occurrence of parasitic infection was significantly higher (P<0.05) in Rohtak followed by Bhiwani, Ambala and the least in Mahendragarh district of Haryana. However, no significant difference (P>0.05) between the cattle and buffaloes of geographical regions was observed. Further, analysis of month, season and age influences on prevalence of GI parasites were found to have no significant impact (P>0.05). Overall, this study helps to assess the parasitic load within the study region and helps to further devise control strategies against the parasites of bovines.

RNA viromes of Dermacentor nuttalli ticks reveal a novel uukuvirus in Qīnghăi Province, China

Ticks are a major parasite on the Qīnghăi-Tibet Plateau, western China, and represent an economic burden to agriculture and animal husbandry. Despite research on tick-borne pathogens that threaten humans and animals, the viromes of dominant tick species in this area remain unknown. In this study, we collected Dermacentor nuttalli ticks near Qīnghăi Lake and identified 13 viruses belonging to at least six families through metagenomic sequencing. Four viruses were of high abundance in pools, including Xīnjiāng tick-associated virus 1 (XJTAV1), and three novel viruses: Qīnghăi Lake virus 1, Qīnghăi Lake virus 2 (QHLV1, and QHLV2, unclassified), and Qīnghăi Lake virus 3 (QHLV3, genus Uukuvirus of family Phenuiviridae in order Bunyavirales), which lacks the M segment. The minimum infection rates of the four viruses in the tick groups were 8.2%, 49.5%, 6.2%, and 24.7%, respectively, suggesting the prevalence of these viruses in D. ​nuttalli ticks. A putative M segment of QHLV3 was identified from the next-generation sequencing data and further characterized for its signal peptide cleavage site, N-glycosylation, and transmembrane region. Furthermore, we probed the L, M, and S segments of other viruses from sequencing data of other tick pools by ​using the putative M segment sequence of QHLV3. By revealing the viromes of D. nuttalli ticks, this study enhances our understanding of tick-borne viral communities in highland regions. The putative M segment identified in a novel uukuvirus suggests that previously identified uukuviruses without M segments should have had the same genome organization as typical bunyaviruses. These findings will facilitate virus discovery and our understanding of the phylogeny of tick-borne uukuviruses.

In silico prediction of CD8+ and CD4+ T cell epitopes in Leishmania major proteome: Using immunoinformatics

The leishmaniases are NDTs (neglected tropical diseases) that affect people all over the world. They are brought on by protozoans from the genus Leishmania and disseminated by phlebotomine flies that are afflicted with the disease. The best option to manage and lower the incidence of these diseases has been thought by the creation of a safe and effective vaccination. This research used an in silico based mining approach to look for high potential epitopes that might bind to MHC Class I and MHC Class II molecules (mainly; HLA-A*02:01 & HLA-DRB1*03:01) from human population in order to promote vaccine development. Based on the presence of signal peptides, GPI anchors, antigenicity predictions, and a subtractive proteomic technique, we have screened 17 putative antigenic proteins from the 8083 total proteins of L. major. After that thorough immunogenic epitope prediction were done using IEDB-AR tools. We isolated five immunogenic epitopes (three 9-mer & two 15-mer) from five antigenic proteins through docking and MD simulation analysis. Finally, these five anticipated epitopes, viz., TLPEIPVNV, ELMAPVFGL, TLAAAVALL, NSINIRLDGVTSAGF and NVPLVVDASSLFRVA have considerably stronger binding potential with their respective alleles and may trigger immunological responses. The goal of this work was to identify MHC restricted epitopes for CD8+ and CD4+ T cells activation using immunoinformatics in order to identify potential vaccine candidates against L. major parasites.

Activity of (η6-arene)dichloridoruthenium(II) complexes with antifungal imidazolyl-based ligands against Toxoplasma gondii and Leishmania major

A series of six (η6-arene)Ru(II) complexes with antifungal imidazole drug ligands such as clotrimazole, bifonazole and climbazole was prepared and analyzed. They were tested for their activities against Leishmania major and Toxoplasma gondii parasites, and were compared with the activities of the metal-free azole ligands. Activities superior to those of the azole ligands were observed for the Ru complexes, which indicate the beneficial role of the (η6-arene)ruthenium(II) moiety in terms of antiparasitic properties. The modifications of the arene ligand also played a role in the biological activity. Docking of selected ruthenium complexes into T. gondii kinase CDPK1 and ADME-T calculations revealed promising binding affinities and drug-like properties.

Glycophorin B-PfEMP1 interaction mediates robust rosetting in Plasmodium falciparum

P. falciparumerythrocyte membrane protein 1 (PfEMP1) is the major parasite protein responsible for rosetting by binding to host receptors such as heparan sulfate, CR1 on RBC surface. Usually monomeric protein-carbohydrate interactions are weak [1], therefore PfEMP1 binds to plasma proteins like IgM or α2-macroglobulin that facilitate its clustering on parasitized RBC surface and augment rosetting [2,3]. We show that 3D7A expresses PfEMP1, PF3D7_0412900, and employs its CIDRγ2 domain to interact with glycophorin B on uninfected RBC to form large rosettes but more importantly even in the absence of plasma proteins. Overall, we established the role of PF3D7_0412900 in rosetting as antibodies against CIDRγ2 domain reduced rosetting and also identified its receptor, glycophorin B which could provide clue why glycophorin B null phenotype, S-s-U- RBCs prevalent in malaria endemic areas is protective against severe malaria.