Molecular And Biochemical Parasitology[JOURNAL]
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200 papers
Characterization of the major surface glycoconjugates of Trypanosoma theileri.
Nagar R, Hambleton I, Tinti M … +2 more , Carrington M, Ferguson MAJ
Mol Biochem Parasitol · 2023 Dec · PMID 37652240 · Full text
Trypanosoma theileri maintains a long-term extracellular infection with a low parasitaemia in bovids. The surface of this parasite is predicted to be decorated with several surface molecules including membrane surface pr...
Trypanosoma theileri maintains a long-term extracellular infection with a low parasitaemia in bovids. The surface of this parasite is predicted to be decorated with several surface molecules including membrane surface proteases (MSPs), trans-sialidases and T. theileri putative surface proteins (TTPSPs). However, there are no experimental data to verify this hypothesis. Here, we have purified and partially characterized the surface glycoconjugates of T. theileri using biochemical and mass spectrometry-based approaches. The glycoconjugates fall into two classes: glycoproteins and glycolipids. Proteomic analysis of the glycoprotein fraction demonstrated the presence of MSPs and abundant mucin-like TTPSPs, with most predicted to be GPI-anchored. Mass spectrometric characterization of the glycolipid fraction showed that these are mannose- and galactose-containing glycoinositolphospholipids (GIPLs) that are larger and more diverse than those of its phylogenetic relative T. cruzi, containing up to 10 hexose residues and carrying either alkylacyl-phosphatidylinositol or inositol-phospho-ceramide (IPC) lipid components.
Characterisation of TcFUT1, a mitochondrial fucosyltransferase from Trypanosoma cruzi.
Paredes Franco JC, Sampaio Guther ML, Lima ML … +1 more , Ferguson MAJ
Mol Biochem Parasitol · 2023 Dec · PMID 37652239 · Publisher ↗
Previous work has shown that the TbFUT1 and LmjFUT1 genes encode essential fucosyltransferases located inside the single mitochondria of the protozoan parasites Trypanosoma brucei and Leishmania major, respectively. Howe...
Previous work has shown that the TbFUT1 and LmjFUT1 genes encode essential fucosyltransferases located inside the single mitochondria of the protozoan parasites Trypanosoma brucei and Leishmania major, respectively. However, nothing was known about the orthologous gene TcFUT1 or its gene product in Trypanosoma cruzi, aetiological agent of Chagas disease. In this study, we describe the overexpression of TcFUT1 with a C-terminal 6xMyc epitope tag in T. cruzi epimastigote cells. Overexpressed and immunoprecipitated TcFUT1-6xMyc was used to demonstrate enzymatic activity and to explore substrate specificity. This defined TcFUT1 as a GDP-Fuc : βGal α1-2 fucosyltransferase with a strict requirement for acceptor glycans with non-reducing terminal Galβ1-3GlcNAc structures. This differs from the specificity of the T. brucei orthologue TbFUT1, which can also tolerate non-reducing terminal Galβ1-4GlcNAc and Galβ1-4Glc acceptor sites. Immunofluorescence microscopy using α-Myc tag antibodies also showed a mitochondrial location for TcFUT1 in T. cruzi epimastigote cells. Collectively, these results are like those described for TbFUT1 and LmjFUT1 from T. brucei and L. major, suggesting that FUT1 gene products have conserved function for across the trypanosomatids and may share therapeutic target potential.
Does hydrogen peroxide contribute to the immunity against Malaria induced by whole attenuated plasmodial sporozoites?
Douradinha B
Mol Biochem Parasitol · 2023 Dec · PMID 37604406 · Publisher ↗
Plasmodium sporozoites can block apoptotic pathways within host hepatocytes, ensuring the survival of the parasite. However, attenuated plasmodial sporozoites are unable to prevent apoptosis, which provides many parasite...
Plasmodium sporozoites can block apoptotic pathways within host hepatocytes, ensuring the survival of the parasite. However, attenuated plasmodial sporozoites are unable to prevent apoptosis, which provides many parasite antigens to immune cells. This exposure leads to protection against Malaria in both human and animal models. If these hosts are later inoculated with infectious sporozoites, apoptosis of infected hepatocytes will occur, preventing parasite development. Considering that hydrogen peroxide can induce apoptosis, it is plausible that it plays a role in the mechanisms associated with the protection mediated by attenuated plasmodial sporozoites. Based on published results that describe the relationship between Plasmodium, hydrogen peroxide, and apoptosis, a rational explanation can be provided for this hypothesis.
Novel anti-Acanthamoebic properties of raloxifene sulfonate/sulfamate derivatives.
Siddiqui R, El-Gamal MI, Sajeev S … +2 more , Zaraei SO, Khan NA
Mol Biochem Parasitol · 2023 Dec · PMID 37562558 · Publisher ↗
Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active tro...
Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active trophozoite to a resistant cyst form is not well understood; the cyst stage is often resistant to chemotherapy, which is of concern given the rise of contact lens use and the ineffective disinfectants available, versus the cyst stage. Herein, for the first time, a range of raloxifene sulfonate/sulfamate derivatives which target nucleotide pyrophosphatase/phosphodiesterase enzymes, were assessed using amoebicidal and excystation tests versus the trophozoite and cyst stage of Acanthamoeba. Moreover, the potential for cytopathogenicity inhibition in amoebae was assessed. Each of the derivatives showed considerable anti-amoebic activity as well as the ability to suppress phenotypic switching (except for compound 1a). Selected raloxifene derivatives reduced Acanthamoeba-mediated host cell damage using lactate dehydrogenase assay. These findings suggest that pyrophosphatase/phosphodiesterase enzymes may be valuable targets against Acanthamoeba infections.
Amino acid usage and protein expression levels in the flatworm Schistosoma mansoni.
Lamolle G, Iriarte A, Simón D … +1 more , Musto H
Mol Biochem Parasitol · 2023 Sep · PMID 37478919 · Publisher ↗
Schistosoma mansoni is a parasitic flatworm that causes a human disease called schistosomiasis, or bilharzia. At the genomic level, S. mansoni is AT-rich, but has some compositional heterogeneity. Indeed, some regions of...
Schistosoma mansoni is a parasitic flatworm that causes a human disease called schistosomiasis, or bilharzia. At the genomic level, S. mansoni is AT-rich, but has some compositional heterogeneity. Indeed, some regions of its genome are GC-rich, mainly in the regions located near the extreme ends of the chromosomes. Recently, we showed that, despite the strong bias towards A/T ending codons, highly expressed genes tend to use GC-rich codons. Here, we address the following question: are highly expressed sequences biased in their amino acid frequencies? Our analyses show that these sequences in S. mansoni, as in species ranging from bacteria to human, are strongly biased in nucleotide composition. Highly expressed genes tend to use GC-rich codons (in the first and second codon positions), which code the energetically cheapest amino acids. Therefore, we conclude that amino acid usage, at least in highly expressed genes, is strongly shaped by natural selection to avoid energetically expensive residues. Whether this is an adaptation to the parasitic way of life of S. mansoni, is unclear since the same pattern occurs in free-living species.
Evaluation of PEN2-ATP6AP1 axis as an antiparasitic target for metformin based on phylogeny analysis and molecular docking.
Liu C, Zhang S, Xue J … +2 more , Zhang H, Yin J
Mol Biochem Parasitol · 2023 Sep · PMID 37473813 · Publisher ↗
BACKGROUND: Metformin (Met), the first-line drug used in the treatment for type 2 diabetes mellitus, is effective against a variety of parasites. However, the molecular target of Met at clinical dose against various para...
BACKGROUND: Metformin (Met), the first-line drug used in the treatment for type 2 diabetes mellitus, is effective against a variety of parasites. However, the molecular target of Met at clinical dose against various parasites remains unclear. Recently, low-dose Met (clinical dose) has been reported to directly bind PEN2 (presenilin enhancer protein 2) and initiate the lysosomal glucose-sensing pathway for AMPK activation via ATP6AP1 (V-type proton ATPase subunit S1), rather than perturbing AMP/ATP levels. METHODS: To explore the possibility of PEN2-ATP6AP1 axis as a drug target of Met for the treatment of parasitic diseases, we identified and characterized orthologs of PEN2 and ATP6AP1 genes in parasites, by constructing phylogenetic trees, analyzing protein sequences and predicting interactions between Met and parasite PEN2. RESULTS: The results showed that PEN2 and ATP6AP1 genes are only found together in a few of parasite species in the cestoda and nematoda groups. Indicated by molecular simulation, Met might function by interacting with PEN2 on V37/W38/E5 (Trichinella spiralis) with similar binding energy, and on F35/S39 (Caenorhabditis elegans) with higher binding energy, comparing to human PEN2. Hence, these results indicated that only the T. spiralis PEN2-ATP6AP1 axis has the potential to be the direct target of low-concentration Met. Together with contribution of host cells including immune cells in vivo, T. spiralis PEN2-ATP6AP1 axis might play roles in reducing parasite load at low-concentration Met. However, the mechanisms of low-concentration Met on other parasitic infections might be mainly achieved by regulating host cells, rather than directly targeting PEN2-ATP6AP1 axis. CONCLUSIONS: These findings revealed the potential mechanisms by which Met treats various parasitic diseases, and shed new light on the development of antiparasitic drugs.
Coenzyme Q10 exhibits anti-inflammatory and immune-modulatory thereby decelerating the occurrence of experimental cerebral malaria.
Nyariki JN, Kimani NM, Kibet PS … +2 more , Kinuthia GK, Isaac AO
Mol Biochem Parasitol · 2023 Sep · PMID 37385350 · Publisher ↗
Cerebral Malaria (CM) is associated with the complex neurological syndrome, whose pathology is mediated by severe inflammatory processes following infection with Plasmodium falciparum. Coenzyme-Q (Co-Q) is a potent anti-...
Cerebral Malaria (CM) is associated with the complex neurological syndrome, whose pathology is mediated by severe inflammatory processes following infection with Plasmodium falciparum. Coenzyme-Q (Co-Q) is a potent anti-inflammatory, anti-oxidant, and anti-apoptotic agent with numerous clinical applications. The aim of this study was to elucidate the role of oral administration of Co-Q on the initiation or regulation of inflammatory immune response during experimental cerebral malaria (ECM). For this purpose, the pre-clinical effect of Co-Q was evaluated in C57BL/6 J mice infected with Plasmodium berghei ANKA (PbA). Treatment with Co-Q resulted in the reduction of infiltrating parasite load, greatly improved the survival rate of PbA-infected mice that occurred independent of parasitaemia and prevented PbA-induced disruption of the blood-brain barrier (BBB) integrity. Exposure to Co-Q resulted in the reduction of infiltration of effector CD8 + T cells in the brain and secretion of cytolytic Granzyme B molecules. Notably, Co-Q-treated mice had reduced levels of CD8 +T cell chemokines CXCR3, CCR2, and CCR5 in the brain following PbA-infection. Brain tissue analysis showed a reduction in the levels of inflammatory mediators TNF- α, CCL3, and RANTES in Co-Q administered mice. In addition, Co-Q modulated the differentiation and maturation of both splenic and brain dendritic cells and cross-presentation (CD8α+DCs) during ECM. Remarkably, Co-Q was very effective in decreasing levels of CD86, MHC-II, and CD40 in macrophages associated with ECM pathology. Exposure to Co-Q resulted in increased expression levels of Arginase-1 and Ym1/chitinase 3-like 3, which is linked to ECM protection. Furthermore, Co-Q supplementation prevented PbA-induced depletion of Arginase and CD206 mannose receptor levels. Co-Q abrogated PbA-driven elevation in pro-inflammatory cytokines IL-1β, IL-18, and IL-6 levels. In conclusion, the oral supplementation with Co-Q decelerates the occurrence of ECM by preventing lethal inflammatory immune responses and dampening genes associated with inflammation and immune-pathology during ECM, and offers an inimitable opening for developing an anti-inflammatory agent against cerebral malaria.
Anti-parasitic activity of a chimeric peptide Cecropin A (2-8)-Melittin (6-9) (CM11) against tachyzoites of Toxoplasma gondii and the BALB/c mouse model of acute toxoplasmosis.
Abbasali Z, Pirestani M, Dalimi A … +2 more , Badri M, Fasihi-Ramandi M
Mol Biochem Parasitol · 2023 Sep · PMID 37348706 · Publisher ↗
Toxoplasmosis is a zoonotic disease that infects most animals, including humans. Pyrimethamine/sulfadiazine is the standard treatment for toxoplasmosis. Although this treatment has been successful, it is often associated...
Toxoplasmosis is a zoonotic disease that infects most animals, including humans. Pyrimethamine/sulfadiazine is the standard treatment for toxoplasmosis. Although this treatment has been successful, it is often associated with side effects that cannot be tolerated. Therefore, various compounds have been proposed as alternative treatments for toxoplasmosis. Antimicrobial peptides (AMPs) act on various pathogens, from viruses to protozoa. The purpose of the present study was to evaluate the effects of CM11 on in vitro and in vivo Toxoplasma gondii infection. For in vitro experiments, VERO cells were treated with different concentrations of CM11 (1-128 μg/ml) compared to sulfadiazine (SDZ) (0.78-100 μg/ml). MTT and lactate dehydrogenase (LDH) assays evaluated the cell viability and plasma membrane integrity. Then, the inhibitory concentration (IC) values were determined for treating tachyzoites of T. gondii before or on cells previously infected. Annexin V-FITC/propidium iodide (PI) staining was used to distinguish viable and apoptotic cells. The effect of CM11, SDZ, and a combination of CM11 and SDZ was evaluated in the BALB/c mouse model of acute toxoplasmosis. CM11 was effective on tachyzoites of T. gondii and had a time and dose-dependent manner. The results of the MTT assay showed that the CC values of CM11 and SDZ were estimated at 17.4 µg/ml and 62.3 µg/ml after 24-h, respectively. The inhibitory concentration (IC) of CM11 and SDZ on infected cells was estimated at 1.9 µg/ml and 1.4 µg/ml after 24-h, respectively. The highest rate of apoptosis (early and late) in high concentrations of SDZ and CM11 was determined for tachyzoites (2.13 % and 13.88 %), non-infected VERO cells (6.1 % and 19.76 %), and infected VERO cells (7.45 % and 29.9 %), respectively. Treating infected mice with CM11 and a combination of CM11 and SDZ had increased survival time. Based on the mentioned results, it can be concluded that CM11 has a beneficial effect on tachyzoites of T. gondii in vitro. The result of the mouse model suggests that CM11, either alone or in combination with other chemotherapeutic agents, could be a potential therapeutic for toxoplasmosis. Hence, antimicrobial peptides could be applied as promising anti-toxoplasma agents for treating toxoplasmosis.
Therapeutic activity of eugenol towards mitigation of anaemia and oxidative organ damage caused by Plasmodium berghei.
Suleiman MA, Usman MA, Awogbamila SO … +3 more , Idris UA, Ibrahim FB, Mohammed HO
Mol Biochem Parasitol · 2023 Sep · PMID 37329986 · Publisher ↗
The parasite responsible for causing malaria infection, Plasmodium, is known to exhibit resistance to a number of already available treatments. This has prompted the continue search for new antimalarial drugs ranging fro...
The parasite responsible for causing malaria infection, Plasmodium, is known to exhibit resistance to a number of already available treatments. This has prompted the continue search for new antimalarial drugs ranging from medicinal plant parts to synthetic compounds. In lieu of this, the mitigative action of the bioactive compound, eugenol towards P. berghei-induced anaemia and oxidative organ damage was investigated following a demonstration of in vitro and in vivo antiplasmodial effects. Mice were infected with chloroquine-sensitive strain of P. berghei and thereafter treated with eugenol at doses of 10 and 20 mg/kg body weight (BW) for seven days. The packed cell volume and redox sensitive biomarkers in the liver, brain and spleen were measured. Our result demonstrated that eugenol significantly (p < 0.05) ameliorated the P. berghei-associated anaemia at a dose of 10 mg/kg BW. In addition, the compound, at a dose of 10 mg/kg BW, significantly (p < 0.05) alleviated the P. berghei-induced organ damage. This evidently confirmed that eugenol plays an ameliorative role towards P. berghei-related pathological alterations. Hence, the study opens up a new therapeutic use of eugenol against plasmodium parasite.
Disruption of a DNA fragment that encodes the microneme adhesive repeat domain-containing region of the BBOV_III011730 does not affect the blood stage growth of Babesia bovis in vitro.
Tuvshintulga B, Guswanto A, Nugraha AB … +3 more , Sivakumar T, Umemiya-Shirafuji R, Yokoyama N
Mol Biochem Parasitol · 2023 Sep · PMID 37315901 · Publisher ↗
Babesia bovis, an intraerythrocytic hemoprotozoan parasite, causes the most pathogenic form of bovine babesiosis, negatively impacting the cattle industry. Comprehensive knowledge of B. bovis biology is necessary for dev...
Babesia bovis, an intraerythrocytic hemoprotozoan parasite, causes the most pathogenic form of bovine babesiosis, negatively impacting the cattle industry. Comprehensive knowledge of B. bovis biology is necessary for developing control methods. In cattle, B. bovis invades the red blood cells (RBCs) and reproduces asexually. Micronemal proteins, which bind to sialic acid of host cells via their microneme adhesive repeat (MAR) domains, are believed to play a key role in host cell invasion by apicomplexan parasites. In this study, we successfully deleted the region encoding MAR domain of the BBOV_III011730 by integrating a fusion gene of enhanced green fluorescent protein-blasticidin-S-deaminase into the genome of B. bovis. The transgenic B. bovis, lacking the MAR domain of the BBOV_III011730, invaded bovine RBCs in vitro and grew at rates similar to the parental line. In conclusion, our study revealed that the MAR domain is non-essential for the intraerythrocytic development of B. bovis in vitro.
Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella.
Zhou BH, Ding HY, Yang JY … +3 more , Chai J, Guo HW, Tian EJ
Mol Biochem Parasitol · 2023 Sep · PMID 37302489 · Publisher ↗
Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target...
Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected. mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.
Transgenic overexpression of heat shock protein (HSP83) enhances protein kinase A activity, disrupts GP63 surface protease expression and alters promastigote morphology in Leishmania amazonensis.
Nation CS, Stephany-Brassesco I, Kelly BL … +1 more , Pizarro JC
Mol Biochem Parasitol · 2023 Sep · PMID 37150327 · Publisher ↗
Leishmania parasites undergo morphological changes during their infectious life cycle, including developmental transitions within the sandfly vector, culminating in metacyclic stages that are pre-adapted for infection. U...
Leishmania parasites undergo morphological changes during their infectious life cycle, including developmental transitions within the sandfly vector, culminating in metacyclic stages that are pre-adapted for infection. Upon entering vertebrate host phagocytes, Leishmania differentiate into intracellular amastigotes, the form that is ultimately transmitted back to the vector to complete the life cycle. Although environmental conditions that induce these cellular transitions are well-established, molecular mechanisms governing Leishmania morphologic differentiation in response to these cues remain largely uncharacterized. Previous studies indicate a key role for HSP83 in both promastigote metacyclogenesis and amastigote differentiation. To further elucidate HSP83 functions in the Leishmania lifecycle, we examined the biological impact of experimentally elevating HSP83 gene expression in Leishmania. Significantly, HSP83 overexpression was associated with altered metacyclic morphology, increased protein kinase A (PKA) activity and decreased expression of the Leishmania major surface protease, GP63. Corroborating these findings, overexpression of the L. amazonensis PKA catalytic subunit resulted in a largely similar phenotype. Our findings demonstrate for the first time in Leishmania, a functional link between HSP83 and PKA in the control of Leishmania gene expression, replication and morphogenesis.
Current status and progress in the omics of Clonorchis sinensis.
Wang N, Zhang Z, Huang L … +3 more , Chen T, Yu X, Huang Y
Mol Biochem Parasitol · 2023 Sep · PMID 37127222 · Publisher ↗
Clonorchis sinensis (C. sinensis) is a fish-borne trematode that inhabits the bile duct of mammals including humans, cats, dogs, rats, and so on. In the complex life cycle of C. sinensis, the worm develops successively i...
Clonorchis sinensis (C. sinensis) is a fish-borne trematode that inhabits the bile duct of mammals including humans, cats, dogs, rats, and so on. In the complex life cycle of C. sinensis, the worm develops successively in two intermediate hosts in fresh water and one definitive host. What's more, it undergoes eight developmental stages with a distinct morphology. Clonorchiasis, caused by C. sinensis infection, is an important food-borne parasitic disease and one of the most common zoonoses. C. sinensis infection could result in hyperplasia of the bile duct epithelium, obstructive jaundice, gall-stones, cholecystitis and cholangitis, even liver cirrhosis and cholangiocarcinoma. Thus, clonorchiasis is a serious public health problem in endemic areas. Integrated strategies should be adopted in the prevention and control of clonorchiasis due to the epidemiological characteristics. The recent advances in high-throughput technologies have made available the profiling of multiple layers of a biological system, genomics, transcriptomics, proteomics, and metabolomics. These data can help us to get more information about the development, physiology, metabolism, and reproduction of the parasite as well as pathogenesis and parasite-host interactions in clonorchiasis. In the present study, we summarized recent progresses in omics studies on C. sinensis providing insights into the studies and future directions on treating and preventing C. sinensis associated diseases.
Characterization of 21 microsatellite loci for the precocious, grass-shrimp trematode Alloglossidium renale.
Hulke JM, Criscione CD
Mol Biochem Parasitol · 2023 Jun · PMID 37086899 · Publisher ↗
We developed microsatellite markers to use in studying the population genetics of the trematode Alloglossidium renale, a fluke with a precocious life cycle where sexual maturation occurs in a grass shrimp. Among 21 teste...
We developed microsatellite markers to use in studying the population genetics of the trematode Alloglossidium renale, a fluke with a precocious life cycle where sexual maturation occurs in a grass shrimp. Among 21 tested loci in a Mississippi population sample, 14 were polymorphic, 12 of which significantly deviated from Hardy-Weinberg Equilibrium (HWE). We estimated identity disequilibrium (ID) to confirm whether the deviations from HWE were due to significant amounts of selfing or due to technical factors. The selfing rate derived from F was 86.6%, whereas the selfing rate obtained by ID was 83.9%, indicating that the deviation in HWE was due to a high amount of selfing within the population. These markers will be useful for ecological and evolutionary studies of A. renale especially in relation to the interplay of hermaphroditic mating systems, inbreeding depression, and transmission dynamics.
Characteristics of Th9 cells in Schistosoma japonicum-infected C57BL/6 mouse mesenteric lymph node.
Qiu H, Wang R, Xing J … +11 more , Li L, Gao Z, Li J, Fang C, Shi F, Mo F, Liu L, Zhao Y, Xie H, Zhao S, Huang J
Mol Biochem Parasitol · 2023 Jun · PMID 37086898 · Publisher ↗
Interleukin 9 (IL-9) is an effective cytokine secreted by newly defined Th9 cells, which is involved in allergic and infectious diseases. In this study, lymphocytes were isolated from mesenteric lymph node (MLN), spleen,...
Interleukin 9 (IL-9) is an effective cytokine secreted by newly defined Th9 cells, which is involved in allergic and infectious diseases. In this study, lymphocytes were isolated from mesenteric lymph node (MLN), spleen, liver, lung, and Peyer's patches (PP) of C57BL/6 mice 5-6 weeks after S. japonicum infection, intracellular cytokine staining was done to detect the percentage of IL-9-producing CD4 T cells. The qPCR and ELISA were used to verify the content of IL-9 in MLN. The population of IL-9-producing lymphocyte subset was identified by FACS. In addition, the dynamic changes and cytokine profiles of Th9 cells in the MLN of infected mice were detected by FACS. ELISA was used to detect IL-9 induced by soluble egg antigen (SEA) from isolated lymphocytes in mouse MLN. The results showed that the percentage of IL-9-secreting Th9 cells in the MLN of the infected mouse was higher than that in the spleen, liver, lung, or PP. Though CD8 Tc cells, NKT cells, and γδT cells could secrete IL-9, CD4 Th cells were the main source of IL-9 in S. japonicum-infected C57BL/6 mice (P < 0.05). The percentage of Th9 cells in MLN of infected mouse increased from week 3-4, and reached a peak at week 5-6, then began to decrease from week 7-8 (P < 0.05). Moreover, Th9 cells could also secrete a small amount of IL-4, IFN-γ, IL-5, and IL-10. Our results suggested a higher percentage of Th9 cells was induced in the MLN of S. japonicum-infected mice, which might play an important role in the early stage of S. japonicum-induced disease.
Designing a multi-epitope chimeric protein from different potential targets: A potential vaccine candidate against Plasmodium.
Devi SB, Kumar S
Mol Biochem Parasitol · 2023 Sep · PMID 37084957 · Publisher ↗
Malaria is an infectious disease that has been a continuous threat to mankind since the time immemorial. Owing to the complex multi-staged life cycle of the plasmodium parasite, an effective malaria vaccine which is full...
Malaria is an infectious disease that has been a continuous threat to mankind since the time immemorial. Owing to the complex multi-staged life cycle of the plasmodium parasite, an effective malaria vaccine which is fully protective against the parasite infection is urgently needed to deal with the challenges. In the present study, essential parasite proteins were identified and a chimeric protein with multivalent epitopes was generated. The designed chimeric protein consists of best potential B and T cell epitopes from five different essential parasite proteins. Physiochemical studies of the chimeric protein showed that the modeled vaccine construct was thermo-stable, hydrophilic and antigenic in nature. And the binding of the vaccine construct with Toll-like receptor-4 (TLR-4) as revealed by the molecular docking suggests the possible interaction and role of the vaccine construct in activating the innate immune response. The constructed vaccine being a chimeric protein containing epitopes from different potential candidates could target different stages or pathways of the parasite. Moreover, the approach used in this study is time and cost effective, and can be applied in the discoveries of new potential vaccine targets for other pathogens.
In vitro and in vivo evaluation of efficacy of berberine chloride: Phyto-alternative approach against Trypanosoma evansi infection.
Gupta S, Vohra S, Sethi K … +4 more , Rani R, Gupta S, Kumar S, Kumar R
Mol Biochem Parasitol · 2023 Jun · PMID 37084956 · Publisher ↗
Current chemotherapy against the Surra organism, Trypanosoma evansi has several limitations in terms of efficacy, toxicity, availability and emerging resistance. These reasons make the search of new chemo-preventive and...
Current chemotherapy against the Surra organism, Trypanosoma evansi has several limitations in terms of efficacy, toxicity, availability and emerging resistance. These reasons make the search of new chemo-preventive and chemo-therapeutic agent with high potency and low toxicity. Alkaloid phyto-molecules, berberine has shown promising anti-kinetoplastid activity against T. cruzi, T. congolense, T. brucei, Leishmania donovani and L. tropica. However, till date, there is no investigation of therapeutic efficacy of berberine chloride (BC) against T. evansi. The IC value of BC for growth inhibition of T. evansi at 24 h of culture was calculated as 12.15 µM. The specific selectivity index (SSI) of BC was calculated as 19.01 and 10.43 against Vero cell line and Equine PBMC's, respectively. Thirteen drug target genes affecting various metabolic pathways were studied to investigate the mode of trypanocidal action of BC. In transcript analysis, the mRNA expression of arginine kinase 1 remained refractory to exposure with BC, which provides metabolic plasticity in adverse environmental conditions. In contrary, rest all the drug target gene were down-regulated, which indicates that drug severely affect DNA replication, cell proliferation, energy homeostasis, redox homeostasis and calcium homeostasis of T. evansi, leading to the death of parasite in low concentrations. It is the first attempt to investigate in vitro anti-trypanosomal activity of BC against T. evansi. These data imply that phytochemicals as alternative strategies can be explored in the future as an alternative treatment for Surra in animal.
Identification of Omega-class glutathione transferases in helminths of the Taeniidae family.
Miles S, Mourglia-Ettlin G, Fernández V
Mol Biochem Parasitol · 2023 Jun · PMID 37024059 · Publisher ↗
Glutathione transferase enzymes (GSTs) are believed to be a major detoxification system in helminth parasites and have been associated with immunomodulation of the host response. Echinococcus granulosus sensu lato (s.l.)...
Glutathione transferase enzymes (GSTs) are believed to be a major detoxification system in helminth parasites and have been associated with immunomodulation of the host response. Echinococcus granulosus sensu lato (s.l.) is a cestode parasite known to express at least five different GSTs, but no Omega-class enzymes have been reported in this parasite or in any other cestode. Herein we report the identification of a new member of the GST superfamily in E. granulosus s.l., which is phylogenetically related to the Omega-class: EgrGSTO. Through mass spectrometry, we showed that the 237 amino acids protein EgrGSTO is expressed by the parasite. Moreover, we identified homologues of EgrGSTO in other eight members of the Taeniidae family, including E. canadensis, E. multilocularis, E. oligarthrus, Hydatigera taeniaeformis, Taenia asiatica, T. multiceps, T. saginata and T. solium. A manual sequence inspection and rational modification yielded eight Taeniidae's GSTO sequences, each one encoding for a 237 aa polypeptide showing 80.2% overall identity. To the best of our knowledge, this is the first description of genes encoding for Omega-class GSTs in worms belonging to the Taeniidae family -that at least in E. granulosus s.l. is expressed as a protein- suggesting the gene encodes for a functional protein.
Genetic diversity and natural selection of rif gene (PF3D7_1254800) in the Plasmodium falciparum global populations.
Xu SJ, Shen HM, Cui YB … +3 more , Chen SB, Xu B, Chen JH
Mol Biochem Parasitol · 2023 Jun · PMID 36918126 · Publisher ↗
To reveal the genetic characteristics of one member of the Plasmodium falciparum repetitive interspersed family (rif), we sequenced the rif gene (PF3D7_1254800) in 53 field isolates collected from Ghana-imported cases in...
To reveal the genetic characteristics of one member of the Plasmodium falciparum repetitive interspersed family (rif), we sequenced the rif gene (PF3D7_1254800) in 53 field isolates collected from Ghana-imported cases into China and compared them with 350 publicly available P. falciparum rif sequences from global populations. In the Ghana-imported population, the nucleotide diversities were 0.05714 and 0.06616 for the full length and variable region of rif gene, respectively. Meanwhile, 22 and 20 haplotypes were identified for the full length and variable region of rif gene (Hd = 0.843 and 0.838, respectively). Diversity of rif gene in Ghana-imported population was higher than that observed in Cambodia, Thailand, Vietnam, Myanmar, Mali, Ghana, and Senegal populations. In this analysis, we found high genetic diversity of rif gene in global P. falciparum populations and identified 158 haplotypes. Tajima's D-test shows that there are large differences in the direction of selection between the conserved and variable region of rif gene. Tajima's D value for the variable region was 0.20074, indicating that balancing selection existed in this region. We found that the variable region was the main target of selection for positive diversification, and most mutation sites were located in this region. The population structure suggested optimized cluster values of K = 6. The five groups in Ghana-imported population included a unique subpopulation. Our results reveal the dynamics of the rif gene (PF3D7_1254800) in P. falciparum populations, which can aid in the rational design of P. falciparum rif-based vaccines.
A simple alkali lysis method for Plasmodium falciparum DNA extraction from filter paper blood samples.
Xiang Z, Li D, Wang S … +8 more , Shen T, He W, Li M, Zeng W, Chen X, Wu Y, Cui L, Yang Z
Mol Biochem Parasitol · 2023 Jun · PMID 36822514 · Full text
A fast, simple, easy, efficient, and inexpensive method for DNA extraction from malaria parasites collected on filter paper would be very useful for molecular surveillance. The quality and quantity of DNA are critical to...
A fast, simple, easy, efficient, and inexpensive method for DNA extraction from malaria parasites collected on filter paper would be very useful for molecular surveillance. The quality and quantity of DNA are critical to molecular diagnosis and analysis. Here, we developed a simple alkali lysis method for DNA extraction from blood samples on filter paper. The results showed that 10-50 mM NaOH and deionized water all effectively isolated parasite DNA at higher parasitemia, as witnessed by successful PCR amplification, while at a parasitemia of 0.01%, the 10 mM NaOH lysis condition generated the best results. Furthermore, DNA extracted by this method was successfully used to amplify a fragment of > 2000 bp. This method successfully extracted DNA from 1 µl of blood at a parasitemia as low as 0.0001% (equivalent to 5 parasites /µl). The DNA isolated by the 10 mM NaOH lysis method was stable to yield PCR products after storage at 4 °C or - 20 °C for 12 months. These results indicate that this alkali lysis method is simple, effective, sensitive, and inexpensive for isolating stable Plasmodium DNA from dried blood spots on filter paper.
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