Molecular and biochemical parasitology最新文献

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Evaluation of PEN2-ATP6AP1 axis as an antiparasitic target for metformin based on phylogeny analysis and molecular docking 基于系统发育分析和分子对接的PEN2-ATP6AP1轴作为二甲双胍抗寄生虫靶点的评价
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111580
Congshan Liu , Shangrui Zhang , Jian Xue , Haobing Zhang , Jianhai Yin
{"title":"Evaluation of PEN2-ATP6AP1 axis as an antiparasitic target for metformin based on phylogeny analysis and molecular docking","authors":"Congshan Liu ,&nbsp;Shangrui Zhang ,&nbsp;Jian Xue ,&nbsp;Haobing Zhang ,&nbsp;Jianhai Yin","doi":"10.1016/j.molbiopara.2023.111580","DOIUrl":"10.1016/j.molbiopara.2023.111580","url":null,"abstract":"<div><h3>Background</h3><p><span>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 </span><em>via</em><span> ATP6AP1 (V-type proton ATPase subunit S1), rather than perturbing AMP/ATP levels.</span></p></div><div><h3>Methods</h3><p><span>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 </span>protein sequences and predicting interactions between Met and parasite PEN2.</p></div><div><h3>Results</h3><p><span>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 (</span><span><em>Trichinella spiralis</em></span>) with similar binding energy, and on F35/S39 (<span><em>Caenorhabditis elegans</em></span>) with higher binding energy, comparing to human PEN2. Hence, these results indicated that only the <em>T. spiralis</em><span> PEN2-ATP6AP1 axis has the potential to be the direct target of low-concentration Met. Together with contribution of host cells including immune cells </span><em>in vivo</em>, <em>T. spiralis</em><span> 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.</span></p></div><div><h3>Conclusions</h3><p>These findings revealed the potential mechanisms by which Met treats various parasitic diseases, and shed new light on the development of antiparasitic drugs.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111580"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10066220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic activity of eugenol towards mitigation of anaemia and oxidative organ damage caused by Plasmodium berghei 丁香酚对伯氏疟原虫引起的贫血和氧化性器官损伤的治疗作用
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111577
Mukhtar Adeiza Suleiman, Mohammed Aliyu Usman, Samson Olayinka Awogbamila, Umar Adam Idris, Fatima Binta Ibrahim, Halimat-Oyibo Mohammed
{"title":"Therapeutic activity of eugenol towards mitigation of anaemia and oxidative organ damage caused by Plasmodium berghei","authors":"Mukhtar Adeiza Suleiman,&nbsp;Mohammed Aliyu Usman,&nbsp;Samson Olayinka Awogbamila,&nbsp;Umar Adam Idris,&nbsp;Fatima Binta Ibrahim,&nbsp;Halimat-Oyibo Mohammed","doi":"10.1016/j.molbiopara.2023.111577","DOIUrl":"10.1016/j.molbiopara.2023.111577","url":null,"abstract":"<div><p>The parasite responsible for causing malaria infection, <em>Plasmodium</em><span>, is known to exhibit resistance to a number of already available treatments. This has prompted the continue search for new antimalarial drugs<span> ranging from medicinal plant parts to synthetic compounds. In lieu of this, the mitigative action of the bioactive compound, eugenol towards </span></span><em>P. berghei</em>-induced anaemia and oxidative organ damage was investigated following a demonstration of <em>in vitro</em> and <em>in vivo</em> antiplasmodial effects. Mice were infected with chloroquine-sensitive strain of <em>P. berghei</em> 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 (<em>p</em> &lt; 0.05) ameliorated the <em>P. berghei</em>-associated anaemia at a dose of 10 mg/kg BW. In addition, the compound, at a dose of 10 mg/kg BW, significantly (<em>p</em> &lt; 0.05) alleviated the <em>P. berghei</em>-induced organ damage. This evidently confirmed that eugenol plays an ameliorative role towards <em>P. berghei</em>-related pathological alterations. Hence, the study opens up a new therapeutic use of eugenol against plasmodium parasite.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111577"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Designing a multi-epitope chimeric protein from different potential targets: A potential vaccine candidate against Plasmodium 从不同潜在靶点设计多表位嵌合蛋白:一种潜在的疟原虫候选疫苗
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111560
Sanasam Bijara Devi, Sanjeev Kumar
{"title":"Designing a multi-epitope chimeric protein from different potential targets: A potential vaccine candidate against Plasmodium","authors":"Sanasam Bijara Devi,&nbsp;Sanjeev Kumar","doi":"10.1016/j.molbiopara.2023.111560","DOIUrl":"10.1016/j.molbiopara.2023.111560","url":null,"abstract":"<div><p><span>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 </span>T cell<span> 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<span> 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.</span></span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111560"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10385140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transgenic overexpression of heat shock protein (HSP83) enhances protein kinase A activity, disrupts GP63 surface protease expression and alters promastigote morphology in Leishmania amazonensis 热休克蛋白(HSP83)的转基因过表达增强了亚马逊利什曼原虫蛋白激酶A的活性,破坏了GP63表面蛋白酶的表达并改变了前鞭毛虫的形态
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111574
Catherine S. Nation , Isabel Stephany-Brassesco , Ben L. Kelly , Juan C. Pizarro
{"title":"Transgenic overexpression of heat shock protein (HSP83) enhances protein kinase A activity, disrupts GP63 surface protease expression and alters promastigote morphology in Leishmania amazonensis","authors":"Catherine S. Nation ,&nbsp;Isabel Stephany-Brassesco ,&nbsp;Ben L. Kelly ,&nbsp;Juan C. Pizarro","doi":"10.1016/j.molbiopara.2023.111574","DOIUrl":"10.1016/j.molbiopara.2023.111574","url":null,"abstract":"<div><p><span><em>Leishmania</em></span><span> parasites undergo morphological changes during their infectious life cycle, including developmental transitions within the sandfly<span> vector, culminating in metacyclic stages that are pre-adapted for infection. Upon entering vertebrate host phagocytes, </span></span><em>Leishmania</em><span> 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 </span><em>Leishmania</em><span> morphologic differentiation in response to these cues remain largely uncharacterized. Previous studies indicate a key role for HSP83 in both promastigote<span> metacyclogenesis and amastigote differentiation. To further elucidate HSP83 functions in the </span></span><em>Leishmania</em> lifecycle, we examined the biological impact of experimentally elevating HSP83 gene expression in <em>Leishmania</em><span>. Significantly, HSP83 overexpression was associated with altered metacyclic morphology, increased protein kinase A (PKA) activity and decreased expression of the </span><em>Leishmania</em> major surface protease, GP63. Corroborating these findings, overexpression of the <em>L. amazonensis</em><span> PKA catalytic subunit resulted in a largely similar phenotype. Our findings demonstrate for the first time in </span><em>Leishmania</em>, a functional link between HSP83 and PKA in the control of <em>Leishmania</em><span> gene expression, replication and morphogenesis.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111574"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coenzyme Q10 exhibits anti-inflammatory and immune-modulatory thereby decelerating the occurrence of experimental cerebral malaria 辅酶Q10具有抗炎和免疫调节作用,从而减缓实验性脑疟疾的发生
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111579
James Nyabuga Nyariki , Njogu M. Kimani , Peter Shikuku Kibet , Geoffrey K. Kinuthia , Alfred Orina Isaac
{"title":"Coenzyme Q10 exhibits anti-inflammatory and immune-modulatory thereby decelerating the occurrence of experimental cerebral malaria","authors":"James Nyabuga Nyariki ,&nbsp;Njogu M. Kimani ,&nbsp;Peter Shikuku Kibet ,&nbsp;Geoffrey K. Kinuthia ,&nbsp;Alfred Orina Isaac","doi":"10.1016/j.molbiopara.2023.111579","DOIUrl":"10.1016/j.molbiopara.2023.111579","url":null,"abstract":"<div><p><span>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</span><sub>10</sub> (Co-Q<sub>10</sub>) 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<sub>10</sub> on the initiation or regulation of inflammatory immune response during experimental cerebral malaria (ECM). For this purpose, the pre-clinical effect of Co-Q<sub>10</sub> was evaluated in C57BL/6 J mice infected with <span><em>Plasmodium berghei</em><em> ANKA</em></span> (PbA). Treatment with Co-Q<sub>10</sub><span> 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</span><sub>10</sub><span> resulted in the reduction of infiltration of effector CD8 + T cells<span> in the brain and secretion of cytolytic Granzyme B molecules. Notably, Co-Q</span></span><sub>10</sub><span><span>-treated mice had reduced levels of CD8 +T cell chemokines<span><span> CXCR3, </span>CCR2<span>, and CCR5 in the brain following PbA-infection. </span></span></span>Brain tissue<span><span> analysis showed a reduction in the levels of inflammatory mediators TNF- α, CCL3, and </span>RANTES in Co-Q</span></span><sub>10</sub> administered mice. In addition, Co-Q<sub>10</sub> modulated the differentiation and maturation of both splenic and brain dendritic cells and cross-presentation (CD8α+DCs) during ECM. Remarkably, Co-Q<sub>10</sub><span> was very effective in decreasing levels of CD86, MHC-II, and CD40 in macrophages associated with ECM pathology. Exposure to Co-Q</span><sub>10</sub> resulted in increased expression levels of Arginase-1 and Ym1/chitinase 3–like 3, which is linked to ECM protection. Furthermore, Co-Q<sub>10</sub><span> supplementation prevented PbA-induced depletion of Arginase<span> and CD206 mannose receptor levels. Co-Q</span></span><sub>10</sub> abrogated PbA-driven elevation in pro-inflammatory cytokines IL-1β, IL-18, and IL-6 levels. In conclusion, the oral supplementation with Co-Q<sub>10</sub> 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.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111579"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella 双唑脲诱导柔嫩艾美耳球虫第二代裂殖子中CDK相关激酶2的表达。
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111575
Bian-hua Zhou , Hai-yan Ding , Jing-yun Yang , Jun Chai , Hong-wei Guo , Er-jie Tian
{"title":"Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella","authors":"Bian-hua Zhou ,&nbsp;Hai-yan Ding ,&nbsp;Jing-yun Yang ,&nbsp;Jun Chai ,&nbsp;Hong-wei Guo ,&nbsp;Er-jie Tian","doi":"10.1016/j.molbiopara.2023.111575","DOIUrl":"10.1016/j.molbiopara.2023.111575","url":null,"abstract":"<div><p><span><span>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 </span>apicomplexan<span> parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of </span></span><span><em>Eimeria tenella</em></span> (<em>Et</em>CRK2) were detected. mRNA and protein expression levels of <em>Et</em>CRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that <em>Et</em>CRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of <em>Et</em>CRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against <em>E.tenella</em> affects the expression pattern of <em>Et</em>CRK2 molecule, and <em>Et</em>CRK2 is a potential target for new drug development.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111575"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9992117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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 嵌合肽Cecropin a(2−8)-蜂毒素(6−9)(CM11)对弓形虫速殖子和急性弓形虫病BALB/c小鼠模型的抗寄生虫活性
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-09-01 DOI: 10.1016/j.molbiopara.2023.111578
Zahra Abbasali , Majid Pirestani , Abdolhossein Dalimi , Milad Badri , Mahdi Fasihi-Ramandi
{"title":"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","authors":"Zahra Abbasali ,&nbsp;Majid Pirestani ,&nbsp;Abdolhossein Dalimi ,&nbsp;Milad Badri ,&nbsp;Mahdi Fasihi-Ramandi","doi":"10.1016/j.molbiopara.2023.111578","DOIUrl":"10.1016/j.molbiopara.2023.111578","url":null,"abstract":"<div><p><span><span>Toxoplasmosis is a </span>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. </span>Antimicrobial peptides<span> (AMPs) act on various pathogens, from viruses<span> to protozoa.</span></span></p><p>The purpose of the present study was to evaluate the effects of CM11 on in vitro and in vivo <span><em>Toxoplasma gondii</em></span><span><span><span> infection. For in vitro experiments, VERO cells were treated with different concentrations of CM11 (1–128 μg/ml) compared to sulfadiazine<span> (SDZ) (0.78–100 μg/ml). MTT and lactate dehydrogenase (LDH) assays evaluated the </span></span>cell viability and plasma membrane integrity. Then, the </span>inhibitory concentration (IC</span><sub>50</sub><span>) values were determined for treating tachyzoites of </span><em>T. gondii</em><span> 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.</span></p><p>CM11 was effective on tachyzoites of <em>T. gondii</em><span> and had a time and dose-dependent manner. The results of the MTT assay showed that the CC</span><sub>50</sub> 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<sub>50</sub>) 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.</p><p>Based on the mentioned results, it can be concluded that CM11 has a beneficial effect on tachyzoites of <em>T. gondii</em> 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-<span><em>toxoplasma</em></span> agents for treating toxoplasmosis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"255 ","pages":"Article 111578"},"PeriodicalIF":1.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Characterisation of TcFUT1, a mitochondrial fucosyltransferase from Trypanosoma cruzi 克鲁兹锥虫线粒体岩藻糖基转移酶TcFUT1的特性研究
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-08-29 DOI: 10.1016/j.molbiopara.2023.111590
Jose Carlos Paredes Franco, Maria Lucia Sampaio Guther, Marta L. Lima, Michael A.J. Ferguson
{"title":"Characterisation of TcFUT1, a mitochondrial fucosyltransferase from Trypanosoma cruzi","authors":"Jose Carlos Paredes Franco,&nbsp;Maria Lucia Sampaio Guther,&nbsp;Marta L. Lima,&nbsp;Michael A.J. Ferguson","doi":"10.1016/j.molbiopara.2023.111590","DOIUrl":"10.1016/j.molbiopara.2023.111590","url":null,"abstract":"<div><p>Previous work has shown that the <em>TbFUT1</em> and <em>LmjFUT1</em> genes encode essential fucosyltransferases located inside the single mitochondria of the protozoan parasites <em>Trypanosoma brucei</em> and <em>Leishmania major,</em> respectively. However, nothing was known about the orthologous gene <em>TcFUT1</em> or its gene product in <em>Trypanosoma cruzi</em>, aetiological agent of Chagas disease. In this study, we describe the overexpression of TcFUT1 with a C-terminal 6xMyc epitope tag in <em>T. cruzi</em> 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 <em>T. brucei</em> 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 <em>T. cruzi</em> epimastigote cells. Collectively, these results are like those described for TbFUT1 and LmjFUT1 from <em>T. brucei</em> and <em>L. major</em>, suggesting that <em>FUT1</em> gene products have conserved function for across the trypanosomatids and may share therapeutic target potential.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"256 ","pages":"Article 111590"},"PeriodicalIF":1.5,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10200999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of the major surface glycoconjugates of Trypanosoma theileri 泰勒锥虫主要表面糖缀合物的特性
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-08-29 DOI: 10.1016/j.molbiopara.2023.111591
Rupa Nagar , Isobel Hambleton , Michele Tinti , Mark Carrington , Michael A.J. Ferguson
{"title":"Characterization of the major surface glycoconjugates of Trypanosoma theileri","authors":"Rupa Nagar ,&nbsp;Isobel Hambleton ,&nbsp;Michele Tinti ,&nbsp;Mark Carrington ,&nbsp;Michael A.J. Ferguson","doi":"10.1016/j.molbiopara.2023.111591","DOIUrl":"10.1016/j.molbiopara.2023.111591","url":null,"abstract":"<div><p><em>Trypanosoma theileri</em> 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 <em>T. theileri</em> 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 <em>T. theileri</em> 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 <em>T. cru</em>z<em>i</em>, containing up to 10 hexose residues and carrying either alkylacyl-phosphatidylinositol or inositol-phospho-ceramide (IPC) lipid components.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"256 ","pages":"Article 111591"},"PeriodicalIF":1.5,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does hydrogen peroxide contribute to the immunity against Malaria induced by whole attenuated plasmodial sporozoites? 过氧化氢是否有助于对整个减毒疟原虫子实体诱导的疟疾免疫?
IF 1.5 4区 医学
Molecular and biochemical parasitology Pub Date : 2023-08-19 DOI: 10.1016/j.molbiopara.2023.111589
Bruno Douradinha
{"title":"Does hydrogen peroxide contribute to the immunity against Malaria induced by whole attenuated plasmodial sporozoites?","authors":"Bruno Douradinha","doi":"10.1016/j.molbiopara.2023.111589","DOIUrl":"10.1016/j.molbiopara.2023.111589","url":null,"abstract":"<div><p><em>Plasmodium</em><span><span> 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 </span>immune cells<span><span>. 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 </span>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 </span></span><em>Plasmodium</em>, hydrogen peroxide, and apoptosis, a rational explanation can be provided for this hypothesis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"256 ","pages":"Article 111589"},"PeriodicalIF":1.5,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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