Frontiers in parasitology最新文献

{"title":"Development of a rapid and highly sensitive nucleic acid-based diagnostic test for schistosomes, leveraging on identical multi-repeat sequences","authors":"Ombeni Ally, B. Kanoi, S. Kamath, Clement Shiluli, E. M. Ndombi, Maurice Odiere, Gerald Misinzo, S. Nyanjom, Chunduri Kiran Kumar, Lucy Ochola, Srinivasa Raju Lolabattu, Jesse Gitaka","doi":"10.3389/fpara.2024.1361493","DOIUrl":"https://doi.org/10.3389/fpara.2024.1361493","url":null,"abstract":"Schistosomiasis (Bilharzia), a neglected tropical disease caused by Schistosoma parasites, afflicts over 240 million people globally, disproportionately impacting Sub-Saharan Africa. Current diagnostic tests, despite their utility, suffer from limitations like low sensitivity. Polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR) remain the most common and sensitive nucleic acid amplification tests. Still, the sensitivity of nucleic acid amplification tests is significantly affected by the copy number of amplification targets, resulting in underestimation of true Schistosoma infections, especially in low transmission settings. Additionally, lengthy qPCR run times pose challenges when dealing with large sample volumes and limited resources. In this study, the identical multi-repeat sequences (IMRS) were used as a novel approach to enhance the sensitivity of nucleic acid-based Bilharzia diagnosis.To identify novel genomic repeat regions, we utilized the IMRS algorithm, with modifications to enable larger target region (100-200bp) identification instead of smaller sequences (18-30bp). These regions enabled customised primer-probe design to suit requirements for qPCR assay. To lower the qPCR amplification times, the assay was conducted using fast cycling condition. Regression analysis, and qPCR data visualization was conducted using Python programming.Using Schistosoma mansoni and S. haematobium, we found that IMRS-based qPCR, employing genus-specific primers and TaqMan probes, offers exceptional analytical sensitivity, detecting as little as a single genome copy per microliter within 36 minutes.The lowest concentration of DNA detected using IMRS-based PCR and qPCR represented tenfold improvement over conventional PCR. As part of further development, there is a need to compare IMRS-based qPCR against other qPCR methods for Schistosoma spp. Nonetheless, IMRS-based diagnostics promise a significant advancement in bilharzia diagnosis, particularly in low-transmission settings, potentially facilitating more effective control and treatment strategies.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"8 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140243394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification and transcriptomic characterization of proliferative cells of Mesocestoides corti selectively affected by irradiation","authors":"A. Costábile, María Fernanda Domínguez, Inés Guarnaschelli, M. Preza, U. Koziol, E. Castillo, J. Tort","doi":"10.3389/fpara.2024.1362199","DOIUrl":"https://doi.org/10.3389/fpara.2024.1362199","url":null,"abstract":"Flatworms depend on stem cells for continued tissue growth and renewal during their life cycles, making these cells valuable drug targets. While neoblasts are extensively characterized in the free-living planarian Schmidtea mediterranea, and similar stem cells have been characterized in the trematode Schistosoma mansoni, their identification and characterization in cestodes is just emerging. Since stem cells are generally affected by irradiation, in this work we used this experimental approach to study the stem cells of the model cestode Mesocestoides corti. We found that gamma irradiation produces a dose-dependent decrease in proliferative cells, requiring higher doses than in other flatworms to completely abolish proliferation. The treatment results in the downregulation of candidate marker genes. Transcriptomic studies reveal that several genes downregulated after irradiation are conserved with other flatworms, and are related to cell cycle, DNA replication and repair functions. Furthermore, proliferative cells were isolated by cell sorting and also characterized transcriptomically. We found that the set of genes characteristic of proliferative cells agrees well with those downregulated during irradiation, and have a significant overlap with those expressed in planarian neoblasts or S. mansoni stem cells. Our study highlights that conserved mechanisms of stem cell biology may be functional in flatworms, suggesting that these could be relevant targets to evaluate in the control of parasitic species.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"124 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140078929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiparasitic activity of the iron-containing milk protein lactoferrin and its potential derivatives against human intestinal and blood parasites","authors":"Namrata Anand","doi":"10.3389/fpara.2023.1330398","DOIUrl":"https://doi.org/10.3389/fpara.2023.1330398","url":null,"abstract":"An iron-containing milk protein named lactoferrin (Lf) has demonstrated antiparasitic and immunomodulatory properties against a variety of human parasites. This protein has shown its capability to bind and transport iron molecules in the vicinity of the host–pathogen environment. The ability of parasites to sequester the iron molecule and to increase their pathogenicity and survival depends on the availability of iron sources. Lf protein has suggested a iron chelating effect on parasites iron and, hence, has shown its antiparasitic effect. Since the parasites have a complex life cycle and have developed drug resistance, vaccines and other treatments are a handful. Therefore, therapeutic research focusing on natural treatment regimens that target the parasite and are non-toxic to host cells is urgently needed. The antiparasitic efficacy of Lf protein has been extensively studied over the past 40 years using both in vitro and in vivo studies. This review article highlighted past important studies on Lf protein that revealed its potential antiparasitic activity against various intracellular and extracellular intestinal or blood-borne human parasites. This review article structures the role of Lf protein in its various forms, such as native, peptide, and nanoformulation, laying the groundwork for its function as an antiparasitic agent and its possible known mechanisms of action.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"86 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140423923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination","authors":"Daniel J. Sprague, C. Rohr, Jonathan S. Marchant","doi":"10.3389/fpara.2024.1349623","DOIUrl":"https://doi.org/10.3389/fpara.2024.1349623","url":null,"abstract":"Infections caused by parasitic flatworms impart a significant disease burden. This is well exemplified by the neglected tropical disease schistosomiasis, which afflicts millions of people worldwide. The anti-schistosomal activity of various chemotypes has been known for decades, but the parasite targets of many of these remain undefined. Until recently, this included the current clinical therapy, praziquantel (PZQ). However, the tempo of target discovery has recently gathered pace, with discoveries of schistosome targets for praziquantel (PZQ) and the anthelmintic benzodiazepine, meclonazepam (MCLZ). This steady patter of target illumination has also revealed a pattern in that both PZQ and MCLZ target members of the same ion channel subgroup—transient receptor potential ion channels of the melastatin family (TRPM channels). PZQ activates one member of this family (TRPMPZQ) and MCLZ activates a different channel (TRPMMCLZ). Here, similarities and differences between these two new targets are discussed. These data highlight the need for further study of TRPM channels in parasitic flatworms given their vulnerability to chemotherapeutic attack.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"174 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139841521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination","authors":"Daniel J. Sprague, C. Rohr, Jonathan S. Marchant","doi":"10.3389/fpara.2024.1349623","DOIUrl":"https://doi.org/10.3389/fpara.2024.1349623","url":null,"abstract":"Infections caused by parasitic flatworms impart a significant disease burden. This is well exemplified by the neglected tropical disease schistosomiasis, which afflicts millions of people worldwide. The anti-schistosomal activity of various chemotypes has been known for decades, but the parasite targets of many of these remain undefined. Until recently, this included the current clinical therapy, praziquantel (PZQ). However, the tempo of target discovery has recently gathered pace, with discoveries of schistosome targets for praziquantel (PZQ) and the anthelmintic benzodiazepine, meclonazepam (MCLZ). This steady patter of target illumination has also revealed a pattern in that both PZQ and MCLZ target members of the same ion channel subgroup—transient receptor potential ion channels of the melastatin family (TRPM channels). PZQ activates one member of this family (TRPMPZQ) and MCLZ activates a different channel (TRPMMCLZ). Here, similarities and differences between these two new targets are discussed. These data highlight the need for further study of TRPM channels in parasitic flatworms given their vulnerability to chemotherapeutic attack.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"29 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139781677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of polymerase chain reaction tests in Chagas disease studies","authors":"Norma Bautista-Lopez, M. Ndao","doi":"10.3389/fpara.2024.1292143","DOIUrl":"https://doi.org/10.3389/fpara.2024.1292143","url":null,"abstract":"The Polymerase Chain Reaction (PCR) test is a highly sensitive, specific, and rapid diagnostic tool for Chagas disease. Chagas disease is caused by the protozoan flagellate Trypanosoma cruzi and is endemic to the Americas. While conventional serological methods are still used in the diagnosis of Chagas disease, they are being gradually replaced by molecular methods like PCR. PCR can detect the parasite’s DNA in blood or tissue samples from humans and animals, including asymptomatic infections and animal reservoirs. In a study conducted on a colony of New World monkeys, PCR analysis was found to be superior to conventional screening tools for trypanosome infection, although false negatives can still occur. In clinical studies, PCR has been used to assess the effectiveness of Nifurtimox and Benznidazole in treating acute and chronic Chagas patients. However, the presence of low-grade and intermittent parasitemia in peripheral blood, even in the absence of treatment, renders PCR an unreliable test for evaluating successful treatment. Based on this limiting factor, among others, we do not believe that PCR is an appropriate gold standard test for Chagas in clinical and preclinical studies. Other diagnostic methods, such as serological and biomarker tests, should be used in conjunction with PCR techniques for more accurate diagnosis of Chagas.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"41 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139781651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of polymerase chain reaction tests in Chagas disease studies","authors":"Norma Bautista-Lopez, M. Ndao","doi":"10.3389/fpara.2024.1292143","DOIUrl":"https://doi.org/10.3389/fpara.2024.1292143","url":null,"abstract":"The Polymerase Chain Reaction (PCR) test is a highly sensitive, specific, and rapid diagnostic tool for Chagas disease. Chagas disease is caused by the protozoan flagellate Trypanosoma cruzi and is endemic to the Americas. While conventional serological methods are still used in the diagnosis of Chagas disease, they are being gradually replaced by molecular methods like PCR. PCR can detect the parasite’s DNA in blood or tissue samples from humans and animals, including asymptomatic infections and animal reservoirs. In a study conducted on a colony of New World monkeys, PCR analysis was found to be superior to conventional screening tools for trypanosome infection, although false negatives can still occur. In clinical studies, PCR has been used to assess the effectiveness of Nifurtimox and Benznidazole in treating acute and chronic Chagas patients. However, the presence of low-grade and intermittent parasitemia in peripheral blood, even in the absence of treatment, renders PCR an unreliable test for evaluating successful treatment. Based on this limiting factor, among others, we do not believe that PCR is an appropriate gold standard test for Chagas in clinical and preclinical studies. Other diagnostic methods, such as serological and biomarker tests, should be used in conjunction with PCR techniques for more accurate diagnosis of Chagas.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"345 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139841621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogen presence, prevalence, and diversity in Ixodes scapularis and mammal hosts at their expanding northern range limits","authors":"Kirsten E. Crandall, Jeremy T Kerr, V. Millien","doi":"10.3389/fpara.2023.1272790","DOIUrl":"https://doi.org/10.3389/fpara.2023.1272790","url":null,"abstract":"With climate and land use changes, tick-borne pathogens are expected to become more widely distributed in Canada. Pathogen spread and transmission in this region is modulated by changes in the abundance and distribution of tick and host populations. Here, we assessed the relationships between pathogens detected in Ixodes scapularis and mammal hosts at sites of different levels of disease risk using data from summer field surveys in Ontario and Quebec, Canada. Generalized linear mixed models and ordinal logistic regressions were used to determine the influence of the abundance of I. scapularis and the abundance and diversity of mammal hosts on pathogen presence, prevalence, and diversity. We detected three pathogen species in I. scapularis and small mammals using nested PCRs, namely Borrelia burgdorferi sensu stricto, Babesia odocoilei, and Babesia microti. Depending on the analyzed pathogen, local infection prevalence ranged from 0% to 25.4% in questing ticks and from 0% to 16.7% in small mammal hosts. We detected B. odocoilei in localities beyond its known range limits in southeastern Quebec suggesting ongoing range expansion of this pathogen. Neither the abundance of I. scapularis nor the abundance and diversity of mammal hosts altered local pathogen presence and prevalence, contrary to expectations. However, mammal species richness was a key predictor of the number of pathogen species. Our study demonstrates the need for future surveillance efforts that test questing and feeding I. scapularis of all life stages, as well as their hosts to better determine the spread, transmission, and co-occurrence of tick-borne pathogens in Canada.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"11 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manipulation of mitochondrial poly(A) polymerase family proteins in Trypanosoma brucei impacts mRNA termini processing","authors":"Clara M. Smoniewski, Poorya Mirzavand Borujeni, Marshall Hampton, Austin Petersen, Sean P. Faacks, R. Salavati, Sara L. Zimmer","doi":"10.3389/fpara.2023.1298561","DOIUrl":"https://doi.org/10.3389/fpara.2023.1298561","url":null,"abstract":"RNA-specific nucleotidyltransferases (rNTrs) add nontemplated nucleotides to the 3′ end of RNA. Two noncanonical rNTRs that are thought to be poly(A) polymerases (PAPs) have been identified in the mitochondria of trypanosomes – KPAP1 and KPAP2. KPAP1 is the primary polymerase that adds adenines (As) to trypanosome mitochondrial mRNA 3′ tails, while KPAP2 is a non-essential putative polymerase whose role in the mitochondria is ambiguous. Here, we elucidate the effects of manipulations of KPAP1 and KPAP2 on the 5′ and 3′ termini of transcripts and their 3′ tails. Using glycerol gradients followed by immunoblotting, we present evidence that KPAP2 is found in protein complexes of up to about 1600 kDa. High-throughput sequencing of mRNA termini showed that KPAP2 overexpression subtly changes an edited transcript’s 3′ tails, though not in a way consistent with general PAP activity. Next, to identify possible roles of posttranslational modifications on KPAP1 regulation, we mutated two KPAP1 arginine methylation sites to either mimic methylation or hypomethylation. We assessed their effect on 3′ mRNA tail characteristics and found that the two mutants generally had opposing effects, though some of these were transcript-specific. We present results suggesting that while methylation increases KPAP1 substrate binding and/or initial nucleotide additions, unmethylated KPAP1is more processive. We also present a comprehensive review of UTR termini, and evidence that tail addition activity may change as mRNA editing is initiated. Together, this work furthers our understanding of the role of KPAP1 and KPAP2 on trypanosome mitochondrial mRNA 3′ tail addition, as well as provides more information on mRNA termini processing in general.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":" 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139625729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reticulocyte Binding Protein Homologue 5 is a target of balancing selection in the Plasmodium falciparum population of Papua New Guinea","authors":"M. Naung, Elijah Martin, Wilson Wong, Z. Razook, Digjaya Utama, Andrew J. Guy, Shannon Takala Harrison, A. Cowman, E. Lin, Benson Kiniboro, M. Laman, Ivo Mueller, Alyssa E. Barry","doi":"10.3389/fpara.2023.1288867","DOIUrl":"https://doi.org/10.3389/fpara.2023.1288867","url":null,"abstract":"Plasmodium falciparum Reticulocyte Binding Protein Homologue (RH5), a leading malaria vaccine candidate, is essential for erythrocyte invasion by the parasite, interacting with the human host receptor, basigin. RH5 has a small number of polymorphisms relative to other blood-stage antigens, and in vitro studies have shown that vaccine-induced antibodies raised against RH5 are strain-transcending, however most studies investigating RH5 diversity have been done in Africa. Understanding the genetic diversity and evolution of malaria antigens in other regions is important for their validation as vaccine candidates. In this study the rh5 gene was sequenced in 677 samples from a longitudinal cohort of Papua New Guinean (PNG) children aged 1-3 years. Of 677 samples successfully sequenced, 566 were identified as independent infections (i.e. one of each pair of identical sequences within hosts were removed). A total of 14 non-synonymous polymorphisms were identified, eight that are ‘common’ in the population (minor allele frequency > 1%), with 44 haplotypes ranging in frequency from 1% to 21%. Modeling of common SNPs to the cryo-EM structure of the RH5/CyRPA/RIPR complex mapped them to the Basigin binding site and near the contact point of CyRPA. Tajima’s D analyses of the corresponding nucleotide sequences produced positive values indicating potential hotspots of balancing selection. We attempted to confirm whether these signals were due to immune selection by measuring the rate of polymorphism between independent infections within the same host, and the association with clinical symptoms, however, no such associations were identified. Together these results suggest that while there is evidence of balancing selection driving RH5 diversity in the PNG P. falciparum population, immune escape was not observed within the cohort of young children. Limited immunity and therefore low selective pressure may explain this result, alternatively other evolutionary forces may contribute to balancing selection at the RH5-BSG binding interface in PNG.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"44 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138946588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}