{"title":"Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.","authors":"Yilong Lu, Xiaoning Zhang, Zhiyu Guan, Rui Ji, Fujun Peng, Chunzhen Zhao, Wei Gao, Feng Gao","doi":"10.1051/parasite/2025001","DOIUrl":"10.1051/parasite/2025001","url":null,"abstract":"<p><p>Cryptosporidiosis, caused by a Cryptosporidium infection, is a serious gastrointestinal disease commonly leading to diarrhea in humans. This disease poses a particular threat to infants, young children, and those with weakened immune systems. The treatment of cryptosporidiosis is challenging due to the current lack of an effective treatment or vaccine. Ongoing research is focused on understanding the molecular pathogenesis of Cryptosporidium and developing pharmacological treatments. In this review, we examine the signaling pathways activated by Cryptosporidium infection within the host and their role in protecting host epithelial cells. Additionally, we also review the research progress of chemotherapeutic targets against cryptosporidia-specific enzymes and anti-Cryptosporidium drugs (including Chinese and Western medicinal drugs), aiming at the development of more effective treatments for cryptosporidiosis.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"7"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-02-17DOI: 10.1051/parasite/2025004
Il-Kwon Kim, Chang-Jun Kim, Jeong-Hwan Choi, Hyun Jun Kang, Moon Bo Choi
{"title":"Stylopization by Xenos spp. (Xenidae, Strepsiptera) in invasive alien hornet, Vespa velutina, in South Korea.","authors":"Il-Kwon Kim, Chang-Jun Kim, Jeong-Hwan Choi, Hyun Jun Kang, Moon Bo Choi","doi":"10.1051/parasite/2025004","DOIUrl":"10.1051/parasite/2025004","url":null,"abstract":"<p><p>The invasive hornet Vespa velutina Lepeletier, which first invaded South Korea in 2003, has spread throughout the country, significantly affecting apiaries, ecosystems, and human health. Xenos spp. (Xenidae, Strepsiptera) are primarily parasitic to social wasps, with V. analis being the only known host in Korea. Until recently, no parasites or parasitoids on V. velutina had been discovered. In 2020, strepsipteran parasites were discovered on 11 hornet workers in Andong City, South Korea. These parasites, comprising four larvae and seven pupae, were all male, except for one individual of an undetermined sex. Molecular analysis and morphological examination identified the parasites as Xenos moutoni (du Buysson, 1903) and X. oxyodontes Nakase & Kato, 2013. This marks the first recorded instance of strepsipteran parasites on V. velutina in regions invaded by this hornet. Although the exact infection rate of these parasites could not be determined, it appears that native strepsipteran parasites have adapted to a non-native Vespa species. Stylopization, the condition caused by these parasites, is known to negatively affect hornet colonies: infected workers do not contribute to nest activities, hindering nest development, and infected reproductive individuals (males and new queens) do not mate, which impedes the establishment of new colonies. However, due to the hornet's high reproductive rate and compensatory mechanisms, the overall control effect of the parasites is likely to be minor.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"10"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-02-21DOI: 10.1051/parasite/2025007
Germán Alfredo Gutiérrez-Liberato, Mélanie Duc, Vytautas Eigirdas, Carolina Romeiro Fernandes Chagas
{"title":"Leucocytozoon infections in tits (Aves, Paridae): blood and tissue stages investigated using an integrative approach.","authors":"Germán Alfredo Gutiérrez-Liberato, Mélanie Duc, Vytautas Eigirdas, Carolina Romeiro Fernandes Chagas","doi":"10.1051/parasite/2025007","DOIUrl":"10.1051/parasite/2025007","url":null,"abstract":"<p><p>Leucocytozoon species are cosmopolitan and prevalent avian parasites, with some infections being lethal, mainly due to the exo-erythrocytic development of the parasite in bird tissues. The patterns of exo-erythrocytic development in Leucocytozoon spp. infections in wild birds remain poorly studied. This study investigated the development of Leucocytozoon spp. tissue stages in tits (Paridae). Great tits (Parus major), Blue tits (Cyanistes caeruleus), and Coal tits (Periparus ater) were screened for infections using an integrative approach that consisted of microscopic analysis of thin blood smears, histological techniques, chromogenic in situ hybridization (CISH), PCR-based methods, and phylogenetic analysis. In total, 41 individuals were analyzed (eight naturally infected that were selected and euthanized, and 33 found dead in the wild and opportunistically sampled). Among the naturally infected birds, all individuals that were microscopically positive for Leucocytozoon species were also PCR-positive for these parasites. Co-infections with Plasmodium spp. and Haemoproteus spp. were commonly found, mainly among the opportunistically sampled birds. Two morphotypes were identified, Leucocytozoon majoris (Laveran, 1902) and Leucocytozoon fringillinarum Woodcock, 1910. Tissue stages were present in three birds sampled exclusively during the non-breeding season, two of them with meronts developing in the kidneys and liver, and one individual with a megalomeront in the heart. All the exo-erythrocytic stages were confirmed to be Leucocytozoon spp. by CISH using a Leucocytozoon genus-specific probe. Phylogenetic analysis placed parasite lineages with different morphotypes in separate clades. The developmental patterns of exo-erythrocytic stages of Leucocytozoon spp. in naturally infected passerines are poorly understood, requiring further research.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"13"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-02-26DOI: 10.1051/parasite/2025003
Lei Xiu, Xiaoling Wang, Shaoyun Cheng, Wanling Liu, Lu Wang, Jiaqi Li, Jinrui Zhang, Yaping Xuan, Wei Hu
{"title":"Evaluating the pathogenic and immunological effects of ds-GFP as a control in in vivo RNA interference studies of Schistosoma japonicum.","authors":"Lei Xiu, Xiaoling Wang, Shaoyun Cheng, Wanling Liu, Lu Wang, Jiaqi Li, Jinrui Zhang, Yaping Xuan, Wei Hu","doi":"10.1051/parasite/2025003","DOIUrl":"10.1051/parasite/2025003","url":null,"abstract":"<p><p>Schistosomiasis affects over 250 million people in 78 countries. Despite praziquantel as the primary treatment, concerns about resistance in schistosomes underscore the need for alternative therapies. The success of RNA interference (RNAi) in schistosomes shows promise for identifying potential drug targets to facilitate drug discovery. Meanwhile, double-stranded RNA (dsRNA) is commonly used in functional gene analysis via RNAi, with double-stranded green fluorescent protein (ds-GFP) widely employed as a control in schistosome-related studies. However, the potential for off-target effects of dsRNAs in various biological systems raises concerns about the reliability of conventional controls in schistosome RNAi experiments. Therefore, this study aims to evaluate the safety and suitability of ds-GFP as an RNAi negative control in Schistosoma japonicum. Our data indicate that ds-GFP is innocuous and exerts no discernible impact on the host's physiology and immune responses. Comprehensive evaluations conducted in mice showed no significant alterations in body and organ weights. While a splenic immune response was observed, histopathological examinations of multiple organs confirmed the absence of significant lesions following ds-GFP treatment. Additionally, S. japonicum morphology, reproductive capacity, and host responses to parasite eggs showed no significant variations. Taken together, these findings bolster the endorsement of ds-GFP as an appropriate negative control in S. japonicum RNAi experiments, offering reliable outcomes crucial for advancing research on schistosomiasis and related parasitic diseases.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"16"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular characterization and subtype analysis of Blastocystis sp. in captive wildlife in Henan, China.","authors":"Zhaohui Cui, Xiyao Huang, Sulan Zhang, Kaifang Li, Aili Zhang, Qichen Li, Yutong Zhang, Junqiang Li, Meng Qi","doi":"10.1051/parasite/2025006","DOIUrl":"10.1051/parasite/2025006","url":null,"abstract":"<p><p>Blastocystis sp. is a zoonotic intestinal protozoan that is ubiquitous globally, residing in the gastrointestinal tracts of both humans and various animals. In the present study, a PCR-sequencing tool based on the SSU rRNA gene was employed to investigate the prevalence and subtypes of Blastocystis spp. in 204 fresh fecal samples collected from 20 captive wildlife species from a bird park in Henan Province, Central China. Overall, Blastocystis was present in 13.73% (28 out of 204) of the samples and 25% (5 out of 20) of the species. A total of four zoonotic subtypes of Blastocystis sp. were found: ST1, ST3, ST5, and ST27, with the latter being the most prevalent, accounting for 35.71% (10 out of 28) of the 5 species positive for Blastocystis sp. To the best of our knowledge, this is the first report of Blastocystis ST27 in birds in China, namely bar-headed goose (Anser indicus) and peafowl (Pavo muticus). The data suggest that captive wildlife, particularly those in bird parks, may frequently be infected with this zoonotic pathogen. Consequently, these animals may serve as potential reservoirs for zoonotic infections in humans.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"11"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-03-05DOI: 10.1051/parasite/2025009
Alissa Majoor, Grégory Michel, Pierre Marty, Laurent Boyer, Christelle Pomares
{"title":"Leishmaniases: Strategies in treatment development.","authors":"Alissa Majoor, Grégory Michel, Pierre Marty, Laurent Boyer, Christelle Pomares","doi":"10.1051/parasite/2025009","DOIUrl":"10.1051/parasite/2025009","url":null,"abstract":"<p><p>Leishmaniases are vector-borne parasitic diseases that pose a threat to over 1 billion people worldwide. The parasites target cells of the reticulohistiocytic system, such as macrophages, where they replicate. The disease manifests in various forms, ranging from localized cutaneous leishmaniasis to life-threatening visceral forms, which are fatal in 95% of cases without treatment. Current treatments rely on the invasive administration of toxic and expensive drugs that are increasingly encountering resistance. Therefore, finding alternative treatments for this disease is imperative. This literature review focuses on recent advancements in alternative treatments and aims to present the various strategies designed to address current limitations, including cost, toxicity, off-target effects, administration routes, and the emergence of drug resistance. Starting with an overview of the existing approved treatments and their specific limitations, we categorize treatment development strategies into five key sections: (i) combination therapies using existing approved treatments to enhance efficacy and reduce resistance; (ii) nanoparticle formulations, which enable targeted delivery to infected organs and improved therapeutic efficiency; (iii) drug repositioning, a strategy that has already contributed to the approval of over half of current therapeutic compounds; (iv) immunomodulation, used in conjunction with standard chemotherapies to enhance treatment efficacy and lower relapse rates; and (v) ethnobotanicals, which have demonstrated promising in vitro results by combining low toxicity, immunomodulatory properties, and potent anti-parasitic effects. In summary, this review outlines current strategies in treatment development, emphasizing their advantages over conventional therapies while acknowledging their limitations.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"18"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-01-22DOI: 10.1051/parasite/2024082
Baby Kyi Soe, Saowalak Kaewmee, Chonlada Mano, Urassaya Pattanawong, Nopporn Tipparawong, Padet Siriyasatien, Derek Gatherer, Michael D Urbaniak, Paul A Bates, Narissara Jariyapan
{"title":"Molecular detection of parasites and host preference in wild-caught Culicoides biting midges (Diptera: Ceratopogonidae) in Chiang Mai and Nakhon Si Thammarat Provinces, Thailand.","authors":"Baby Kyi Soe, Saowalak Kaewmee, Chonlada Mano, Urassaya Pattanawong, Nopporn Tipparawong, Padet Siriyasatien, Derek Gatherer, Michael D Urbaniak, Paul A Bates, Narissara Jariyapan","doi":"10.1051/parasite/2024082","DOIUrl":"10.1051/parasite/2024082","url":null,"abstract":"<p><p>Culicoides biting midges (Diptera: Ceratopogonidae) have been reported as potential vectors for haemoparasites. Information about host-vector-parasite specificity is required to confirm their status. Here, molecular detection of haemosporidians, Leishmania, trypanosomatids, and filarial nematodes in biting midges was conducted to understand their potential role as vectors, and their host preference was determined. Wild-caught biting midges were collected from six different localities of Chiang Mai and Nakhon Si Thammarat provinces, Thailand. A total of 6,578 individual Culicoides (170 males, 6,408 females) comprising 15 species of six sub-genera and two groups were collected. Also, 738 parous females and 29 engorged females were examined for parasites and host blood meals, respectively. Culicoides arakawae, C. mahasarakhamense, C. peregrinus and C. innoxius in Chiang Mai province, and C. innoxius and C. peregrinus in Nakhon Si Thammarat province were the most dominant species. Leucocytozoon spp., Leucocytozoon caulleryi and Plasmodium juxtanucleare were identified in five Culicoides species including C. mahasarakhamense, C. arakawae, C. oxystoma, C. fulvus, and C. guttifer. This study is the first record of L. caulleryi in the biting midge C. arakawae in Thailand. Blood meal analysis revealed that Culicoides primarily fed on cattle (17/29, 58.6%), followed by chickens (10/29, 34.5%), and humans (2/29, 6.9%). Our findings confirmed the existence of several Culicoides species in Thailand, which might be potential vectors for transmission of haemosporidians (Leucocytozoon and Plasmodium). Information from host blood meal analyses underlined their preference for large mammals, followed by domestic chickens. More anthropophilic Culicoides species remain to be discovered.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"2"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-01-22DOI: 10.1051/parasite/2024080
Ľudmila Juhásová, Eva Čisovská Bazsalovicsová, Monica Caffara, Alžbeta Radačovská, Andrea Gustinelli, Lucia Dinisová, Yaroslav Syrota, Ivica Králová-Hromadová
{"title":"Population structure of Clinostomum complanatum (Trematoda: Digenea) with new data on haplotype diversity of flukes from Slovakia and Italy.","authors":"Ľudmila Juhásová, Eva Čisovská Bazsalovicsová, Monica Caffara, Alžbeta Radačovská, Andrea Gustinelli, Lucia Dinisová, Yaroslav Syrota, Ivica Králová-Hromadová","doi":"10.1051/parasite/2024080","DOIUrl":"10.1051/parasite/2024080","url":null,"abstract":"<p><p>The fluke Clinostomum complanatum, a parasite of piscivorous birds, but also reptiles and rarely mammals, has established several foci in the western Palaearctic regions. Previous studies pointed out the complicated taxonomy of the genus, but broader population genetic analysis of C. complanatum has not yet been carried out. The aim of this study was to determine the structure, intraspecific variability, and diversity of mitochondrial cox1 haplotypes of C. complanatum from different localities in Slovakia (Danube floodplain forests) and Italy (Emilia-Romagna and Tuscany), as well as to evaluate the interrelationships among populations from Europe, the Middle East, and North Africa. The genetic structure of C. complanatum from Slovakia and Italy was represented by a great number of haplotypes, showing stable populations with high intraspecific diversity. The haplotypes of samples from other localities (Romania, Turkey, Egypt, and Iran) showed possible gene flow among the populations from Central Europe down to the Mediterranean region, North Africa, and the Middle East. The genetic homogeneity of these samples can be linked to the distribution and migratory routes of the definitive hosts, aquatic piscivorous birds, mainly herons and cormorants, that spread parasite eggs among the continents.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"3"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ParasitePub Date : 2025-01-01Epub Date: 2025-02-07DOI: 10.1051/parasite/2024076
Gabriel Simon, Frédéric Grenouillet, Carine Richou, Eric Delabrousse, Oleg Blagoskonov, Anne Minello, Gerard Thiefin, Emilia Frentiu, Martine Wallon, Solange Bresson-Hadni, Paul Calame
{"title":"Correlation between imaging features and rEm18 antibodies in alveolar echinococcosis: results from a multicenter study in France.","authors":"Gabriel Simon, Frédéric Grenouillet, Carine Richou, Eric Delabrousse, Oleg Blagoskonov, Anne Minello, Gerard Thiefin, Emilia Frentiu, Martine Wallon, Solange Bresson-Hadni, Paul Calame","doi":"10.1051/parasite/2024076","DOIUrl":"10.1051/parasite/2024076","url":null,"abstract":"<p><strong>Background: </strong>To correlate imaging features of alveolar echinococcosis (AE) with the antibodies to recombinant Em18 (rEm18AB) at diagnosis and evaluate initial imaging features associated with serologic response, this retrospective study used data from the prospective multicenter EchinoVISTA study (NCT02876146). Imaging and serology were performed at diagnosis and during follow-up. Univariate and multivariate analyses were used to evaluate imaging features associated with the rEm18AB index. Follow-up analyses evaluated the imaging features associated with serologic response (defined as a 50% reduction in the baseline value within 2 years) in non-operated patients treated with albendazole alone.</p><p><strong>Results: </strong>From June 2012 to July 2016, 45 patients were included, with 8/45 (18%) having an rEm18AB index < 1. Maximum lesion size (76 mm [IQR = 57-93] vs. 36 mm [IQR = 26-51], p = 0.006), microcyst percentage (70% [IQR = 3-8] vs. 20% [IQR = 0.5-3.5], p = 0.004), and maximum standardized uptake value (SUV) on fluorodeoxyglucose positron emission tomography (5.1 [IQR = 4.4-6.2] vs. 2.6 [IQR = 2.4-3.9], p = 0.001) were associated with an rEm18AB index > 1. In patients treated with albendazole, serologic responders at 2 years had smaller lesions (5.3 [IQR = 3.8-72] vs. 3.5 [IQR = 2.7-3.7], p = 0.010) with less pedicle involvement, and lower initial rEm18AB index (2.98 ± 1.63 vs. 7.81 ± 3.95, p = 0.011).</p><p><strong>Conclusion: </strong>Maximum lesion size, percentage of microcysts within the lesion, and maximum lesion SUV are significant imaging features of AE correlated with the rEm18AB index. Serologic response at 2 years occurs primarily in patients with small lesions and a low rEm18AB index.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"8"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Apoptotic proteins in Leishmania donovani: in silico screening, modeling, and validation by knock-out and gene expression analysis.","authors":"Ketan Kumar, Lucien Crobu, Rokhaya Thiam, Chandi C Mandal, Yvon Sterkers, Vijay Kumar Prajapati","doi":"10.1051/parasite/2024081","DOIUrl":"10.1051/parasite/2024081","url":null,"abstract":"<p><p>Visceral leishmaniasis, a life-threatening vector-borne illness that disproportionately affects children and elderly immunocompromised people, is a primary tropical neglected disease. No apoptotic partner proteins have yet been reported in Leishmania donovani, while their identification could contribute to knowledge on parasite cell death and the establishment of alternative therapeutics. We searched for mammalian Bcl-2 family protein orthologs and found one anti-apoptotic and two pro-apoptotic orthologs in L. donovani. A pro-death aquaporin protein, due to its characteristic BH3 domain known to interact with pro-apoptotic proteins in mammalian Bcl-2 family proteins, was also included in this study. Molecular docking and molecular dynamics simulations were conducted to assess protein-protein interactions between the identified apoptotic proteins and mimic mammalian intrinsic apoptotic pathways. The results showed that both pro-apoptotic proteins interacted with the hydrophobic pocket of the anti-apoptotic ortholog, forming a stable complex. This interaction may represent a critical event in an apoptotic pathway in L. donovani. To further characterise it, we used CRISPR-Cas9 approaches to target the identified proteins. Pure knocked population mutants, and episomal over-expressing mutant cells were exposed to apoptotic stimuli. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and quantitative expression profiling suggested that these proteins are involved in the parasite's apoptosis and could play a role in its survival.</p>","PeriodicalId":19796,"journal":{"name":"Parasite","volume":"32 ","pages":"9"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}