Pub Date : 2024-10-15DOI: 10.1016/j.exppara.2024.108847
Jose Jesús Flores-Vega , Jonathan Puente-Rivera , Sharon Itzel Sosa-Mondragón , Minerva Camacho-Nuez , María Elizbeth Alvarez-Sánchez
The DNA of protozoan parasites is highly susceptible to damage, either induced by environmental agents or spontaneously generated during cellular metabolism through reactive oxygen species (ROS). Certain phases of the cell cycle, such as meiotic recombination, and external factors like ionizing radiation (IR), ultraviolet light (UV), or chemical genotoxic agents further increase this susceptibility. Among the various types of DNA damage, double-stranded breaks (DSBs) are the most critical, as they are challenging to repair and can result in genetic instability or cell death. DSBs caused by environmental stressors are primarily repaired via one of two major pathways: non-homologous end joining (NHEJ) or homologous recombination (HR). In multicellular eukaryotes, NHEJ predominates, but in unicellular eukaryotes such as protozoan parasites, HR seems to be the principal mechanism for DSB repair. The HR pathway is orchestrated by proteins from the RAD52 epistasis group, including RAD51, RAD52, RAD54, RAD55, and the MRN complex. This review focuses on elucidating the diverse roles and significance of RAD51 recombinase and its paralogs in protozoan parasites, such as Acanthamoeba castellanii, Entamoeba histolytica (Amoebozoa), apicomplexan parasites (Chromalveolata), Naegleria fowleri, Giardia spp., Trichomonas vaginalis, and trypanosomatids (Excavata), where they primarily function in HR. Additionally, we analyze the diversity of proteins involved in HR, both upstream and downstream of RAD51, and discuss the implications of these processes in parasitic protozoa.
原生动物寄生虫的 DNA 极易受到损伤，这种损伤可能是环境因素诱发的，也可能是细胞代谢过程中通过活性氧（ROS）自发产生的。细胞周期的某些阶段，如减数分裂重组，以及电离辐射（IR）、紫外线（UV）或化学基因毒性物质等外部因素，都会进一步增加这种易感性。在各种类型的 DNA 损伤中，双链断裂（DSB）最为关键，因为它们难以修复，可能导致基因不稳定或细胞死亡。环境应激因素造成的 DSB 主要通过两种主要途径之一进行修复：非同源末端连接（NHEJ）或同源重组（HR）。在多细胞真核生物中，NHEJ占主导地位，但在原生动物寄生虫等单细胞真核生物中，HR似乎是DSB修复的主要机制。HR途径由RAD52外显子组的蛋白质协调，包括RAD51、RAD52、RAD54、RAD55和MRN复合体。本综述重点阐明了 RAD51 重组酶及其旁系亲属在原生动物寄生虫（如棘阿米巴、组织溶解恩塔米巴虫（阿米巴原虫）、阿米巴复合寄生虫（Chromalveolata）、福氏瑙格勒氏虫、贾第鞭毛虫属、阴道毛滴虫和锥虫（Excavata））中的不同作用和意义，它们在这些寄生虫中主要发挥 HR 功能。此外，我们还分析了 RAD51 上下游参与 HR 的蛋白质的多样性，并讨论了这些过程对寄生原生动物的影响。
{"title":"RAD51 recombinase and its paralogs: Orchestrating homologous recombination and unforeseen functions in protozoan parasites","authors":"Jose Jesús Flores-Vega , Jonathan Puente-Rivera , Sharon Itzel Sosa-Mondragón , Minerva Camacho-Nuez , María Elizbeth Alvarez-Sánchez","doi":"10.1016/j.exppara.2024.108847","DOIUrl":"10.1016/j.exppara.2024.108847","url":null,"abstract":"<div><div>The DNA of protozoan parasites is highly susceptible to damage, either induced by environmental agents or spontaneously generated during cellular metabolism through reactive oxygen species (ROS). Certain phases of the cell cycle, such as meiotic recombination, and external factors like ionizing radiation (IR), ultraviolet light (UV), or chemical genotoxic agents further increase this susceptibility. Among the various types of DNA damage, double-stranded breaks (DSBs) are the most critical, as they are challenging to repair and can result in genetic instability or cell death. DSBs caused by environmental stressors are primarily repaired via one of two major pathways: non-homologous end joining (NHEJ) or homologous recombination (HR). In multicellular eukaryotes, NHEJ predominates, but in unicellular eukaryotes such as protozoan parasites, HR seems to be the principal mechanism for DSB repair. The HR pathway is orchestrated by proteins from the RAD52 epistasis group, including RAD51, RAD52, RAD54, RAD55, and the MRN complex. This review focuses on elucidating the diverse roles and significance of RAD51 recombinase and its paralogs in protozoan parasites, such as <em>Acanthamoeba castellanii</em>, <em>Entamoeba histolytica</em> (Amoebozoa), apicomplexan parasites (Chromalveolata), <em>Naegleria fowleri</em>, <em>Giardia</em> spp., <em>Trichomonas vaginalis</em>, and trypanosomatids (Excavata), where they primarily function in HR. Additionally, we analyze the diversity of proteins involved in HR, both upstream and downstream of RAD51, and discuss the implications of these processes in parasitic protozoa.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"267 ","pages":"Article 108847"},"PeriodicalIF":1.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461313","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}
Pub Date : 2024-10-15DOI: 10.1016/j.exppara.2024.108846
Y. Ajith , Sasi Adithya , K.S. Athira , V. Beena , M. Saifudeen Safeer , Sabu Mathews Mevin , P. Preena , A.R. Nisha , Mathew Manju , George Arun , S. Ajithkumar
The environment is the most important stratum in the epidemiological triad of a parasitic disease and any variations in the environmental factors may decide the dynamic occurrence and existence of different lifecycle stages of these parasites. The present study investigated the correlations between key biometeorological and demographical parameters with the incidence of different gastrointestinal parasites and hemoparasites among goats. Four hundred and thirty-two goats were screened for parasitic infection in a yearlong survey conducted from July 2022 to June 2023 in the Teaching Veterinary Clinical Complex, Mannuthy, Kerala, India. The weather parameters (Tmax, Tmin, RH, THI, and bright sunshine hours), air quality parameters [AQI, PM2.5, and PM10], and demographic parameters (gender and age) were recorded along with the test positivity of different categories of gastrointestinal parasites and hemoparasites in goats by routine fecal sample examination and blood smear examination, respectively. The infection level was ranked based on the severity of the infection. The mean and daily variations in biometeorological parameters were calculated and the data were statistically analyzed to figure out the pertinent correlations in host-parasite-environment interaction patterns. High levels of parasitic infections with significant month-wise variations and climate-correlated peak infection patterns were noticed. The incidence of parasites was negatively correlated to all parameters except humidity, indicating more severe parasitism during monsoon months. The significant variations in the host-parasite interaction dynamics point towards the need for detailed explorations concerning the lifecycle of each specific parasite with a focus on the possible environment-favourable and resistant lifecycle stages. Future studies may be designed from a biometeorological perspective to develop a crucial understanding of host-parasite-environment interactions in goats ensuring sustainable goat farming.
{"title":"Effects of environmental factors on host-parasite interaction patterns in backyard-tethered goats of Kerala, India","authors":"Y. Ajith , Sasi Adithya , K.S. Athira , V. Beena , M. Saifudeen Safeer , Sabu Mathews Mevin , P. Preena , A.R. Nisha , Mathew Manju , George Arun , S. Ajithkumar","doi":"10.1016/j.exppara.2024.108846","DOIUrl":"10.1016/j.exppara.2024.108846","url":null,"abstract":"<div><div>The environment is the most important stratum in the epidemiological triad of a parasitic disease and any variations in the environmental factors may decide the dynamic occurrence and existence of different lifecycle stages of these parasites. The present study investigated the correlations between key biometeorological and demographical parameters with the incidence of different gastrointestinal parasites and hemoparasites among goats. Four hundred and thirty-two goats were screened for parasitic infection in a yearlong survey conducted from July 2022 to June 2023 in the Teaching Veterinary Clinical Complex, Mannuthy, Kerala, India. The weather parameters (T<sub>max</sub>, T<sub>min</sub>, RH, THI, and bright sunshine hours), air quality parameters [AQI, PM<sub>2.5</sub>, and PM<sub>10</sub>], and demographic parameters (gender and age) were recorded along with the test positivity of different categories of gastrointestinal parasites and hemoparasites in goats by routine fecal sample examination and blood smear examination, respectively. The infection level was ranked based on the severity of the infection. The mean and daily variations in biometeorological parameters were calculated and the data were statistically analyzed to figure out the pertinent correlations in host-parasite-environment interaction patterns. High levels of parasitic infections with significant month-wise variations and climate-correlated peak infection patterns were noticed. The incidence of parasites was negatively correlated to all parameters except humidity, indicating more severe parasitism during monsoon months. The significant variations in the host-parasite interaction dynamics point towards the need for detailed explorations concerning the lifecycle of each specific parasite with a focus on the possible environment-favourable and resistant lifecycle stages. Future studies may be designed from a biometeorological perspective to develop a crucial understanding of host-parasite-environment interactions in goats ensuring sustainable goat farming.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108846"},"PeriodicalIF":1.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441554","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}
Pub Date : 2024-10-15DOI: 10.1016/j.exppara.2024.108848
Gracienhe Gomes dos Santos , Liseth Vanessa Perenguez Riofrio , Maria Clara Miguel Libanori , Paola Capistrano dos Santos , Domickson Silva Costa , Jucimauro de Araújo Pereira Junior , Alexandre Vaz da Silva , Emilly Monteiro Lopes , Ana Paula de Souza , José Luiz Pedreira Mouriño , Diego José Nogueira , Gabriela Tomas Jerônimo , Maurício Laterça Martins
The study aimed to evaluate the in vitro anthelminthic and antimicrobial activity of silver nanoparticles (AgNPs) against Dactylogyrus minutus and Aeromonas hydrophila, pathogens of Cyprinus carpio Koi. Gill arches of the fish were removed and placed into six-well plates containing 10 mL of tank water with varying concentrations of AgNPs: 100, 400, 500, 600, and 800 mg/L, along with control groups using tank water and distilled water. Each group was tested in triplicate. Parasites were observed every 10 min for 300 min (5 h) using a stereomicroscope, and mortality rates were recorded. Anthelminthic efficacy was calculated at the end of the tests. For the in vitro antimicrobial test, the Minimum Inhibitory Concentration (MIC) of AgNPs was determined by adding 100 μL of Poor Broth (PB) culture medium to all 96 wells of a microplate. The first well was filled with 100 μL of AgNPs, followed by serial dilutions (1:2 ratio). Subsequently, 50 μL of A. hydrophila (1 × 107 CFU/mL) was added to all wells and incubated for 24 h at 28 °C. Results showed that 800 mg/L of AgNPs achieved 87% anthelminthic efficacy within 300 min, while 100 mg/L achieved 47% efficacy. The MIC showed bacterial growth inhibition at 125 mg/mL. Despite the 87% efficacy against parasites within 300 min, AgNPs did not reach 100% efficacy quickly, limiting their potential use in ornamental fish farming. Further studies are needed to assess the toxicity of AgNPs in fish.
{"title":"Silver nanoparticles exhibit in vitro anthelmintic and antimicrobial activities against Dactylogyrus minutus (Kulwieć, 1927), and Aeromonas hydrophila in Cyprinus carpio Koi","authors":"Gracienhe Gomes dos Santos , Liseth Vanessa Perenguez Riofrio , Maria Clara Miguel Libanori , Paola Capistrano dos Santos , Domickson Silva Costa , Jucimauro de Araújo Pereira Junior , Alexandre Vaz da Silva , Emilly Monteiro Lopes , Ana Paula de Souza , José Luiz Pedreira Mouriño , Diego José Nogueira , Gabriela Tomas Jerônimo , Maurício Laterça Martins","doi":"10.1016/j.exppara.2024.108848","DOIUrl":"10.1016/j.exppara.2024.108848","url":null,"abstract":"<div><div>The study aimed to evaluate the <em>in vitro</em> anthelminthic and antimicrobial activity of silver nanoparticles (AgNPs) against <em>Dactylogyrus minutus</em> and <em>Aeromonas hydrophila</em>, pathogens of <em>Cyprinus carpio</em> Koi. Gill arches of the fish were removed and placed into six-well plates containing 10 mL of tank water with varying concentrations of AgNPs: 100, 400, 500, 600, and 800 mg/L, along with control groups using tank water and distilled water. Each group was tested in triplicate. Parasites were observed every 10 min for 300 min (5 h) using a stereomicroscope, and mortality rates were recorded. Anthelminthic efficacy was calculated at the end of the tests. For the <em>in vitro</em> antimicrobial test, the Minimum Inhibitory Concentration (MIC) of AgNPs was determined by adding 100 μL of Poor Broth (PB) culture medium to all 96 wells of a microplate. The first well was filled with 100 μL of AgNPs, followed by serial dilutions (1:2 ratio). Subsequently, 50 μL of <em>A</em>. <em>hydrophila</em> (1 × 10<sup>7</sup> CFU/mL) was added to all wells and incubated for 24 h at 28 °C. Results showed that 800 mg/L of AgNPs achieved 87% anthelminthic efficacy within 300 min, while 100 mg/L achieved 47% efficacy. The MIC showed bacterial growth inhibition at 125 mg/mL. Despite the 87% efficacy against parasites within 300 min, AgNPs did not reach 100% efficacy quickly, limiting their potential use in ornamental fish farming. Further studies are needed to assess the toxicity of AgNPs in fish.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"267 ","pages":"Article 108848"},"PeriodicalIF":1.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461314","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}
Pub Date : 2024-10-05DOI: 10.1016/j.exppara.2024.108843
Mai Mahmoud , Amal Farahat Allam , Amina Essawy Essawy , Thanaa Ibrahim Shalaby , Soheir Salem El-Sherif
Praziquantel (PZQ) is the standard treatment for schistosomiasis; however, it is poorly effective on immature and juvenile worms. The present study aimed to evaluate the therapeutic efficacy of praziquantel loaded-chitosan nanoparticles (PZQ-CSNPs) on the 25 days old juvenile Schistosoma mansoni worms compared to PZQ and chitosan nanoparticles (CSNPs). It was conducted on 60 Swiss albino mice, including 20 control and 40 experimental mice. The control groups included healthy uninfected and infected non-treated mice. The experimental groups included mice infected treated on the 25th day with 400 mg/kg PZQ, 30 mg/kg CSNPs, 100 mg/kg, and 400 mg/kg PZQ-CSNPs. The results revealed that PZQ-CSNPs (100, 400 mg/kg) gave the best results substantiated by a remarkable decrease in worm burden, egg count, granuloma count and size compared to the other treatments. Moreover, it induced severe deformations of worm morphology regarding oral and ventral suckers, tegument, spines distribution, and male gynaecophoric canal. Liver enzymes and oxidative stress markers were significantly decreased while antioxidant activities were increased compared to control and other treated groups. In conclusion, a single dose of PZQ-CSNPs had significant antischistosomal therapeutic effects during the early maturation phase.
{"title":"Therapeutic efficacy of praziquantel loaded-chitosan nanoparticles on juvenile Schistosoma mansoni worms in murine model","authors":"Mai Mahmoud , Amal Farahat Allam , Amina Essawy Essawy , Thanaa Ibrahim Shalaby , Soheir Salem El-Sherif","doi":"10.1016/j.exppara.2024.108843","DOIUrl":"10.1016/j.exppara.2024.108843","url":null,"abstract":"<div><div>Praziquantel (PZQ) is the standard treatment for schistosomiasis; however, it is poorly effective on immature and juvenile worms. The present study aimed to evaluate the therapeutic efficacy of praziquantel loaded-chitosan nanoparticles (PZQ-CSNPs) on the 25 days old juvenile <em>Schistosoma mansoni</em> worms compared to PZQ and chitosan nanoparticles (CSNPs). It was conducted on 60 Swiss albino mice, including 20 control and 40 experimental mice. The control groups included healthy uninfected and infected non-treated mice. The experimental groups included mice infected treated on the 25th day with 400 mg/kg PZQ, 30 mg/kg CSNPs, 100 mg/kg, and 400 mg/kg PZQ-CSNPs. The results revealed that PZQ-CSNPs (100, 400 mg/kg) gave the best results substantiated by a remarkable decrease in worm burden, egg count, granuloma count and size compared to the other treatments. Moreover, it induced severe deformations of worm morphology regarding oral and ventral suckers, tegument, spines distribution, and male gynaecophoric canal. Liver enzymes and oxidative stress markers were significantly decreased while antioxidant activities were increased compared to control and other treated groups. In conclusion, a single dose of PZQ-CSNPs had significant antischistosomal therapeutic effects during the early maturation phase.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108843"},"PeriodicalIF":1.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380382","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}
Pub Date : 2024-10-05DOI: 10.1016/j.exppara.2024.108844
Samya Alenezi , Ngozichukwuka P. Igoli , Alexander I. Gray , Enimie E. Oaikhena , Ibrahim A. Alfayez , Harry P. de Koning , John O. Igoli
Ten compounds, six extracts and five fractions obtained from three Nigerian plants were assayed for their in vitro antitrypanosomal and antileishmanial activities. Each plant was extacted with hexane, ethyl acetate, and methanol. Isolated compounds were characterized and identified based on their NMR chemical shifts and comparison to literature reports. The crude extracts, fractions and isolated compounds were tested against the kinetoplastid parasites: bloodstream forms of Trypanosoma brucei Lister 427WT and the derived multi-drug resistant clone B48, and promastigote forms of Leishmania mexicana cas9/T7 and the derived clone cas9ΔNT1. Column chromatography of the extracts using silica gel yielded ten compounds identified as curzerenone, epi-curzerenone, chloranthene F, isofuranodienone, 8(17)-12E-labdadiene-15, 16-dial and 15-hydroxy-8(17),12E-labdadiene-16-al from Siphonochilus aetiopicus, lupeol, linalolic acid and spinasterone from Calliandra portoricensis, and abruquinone B from Abrus precatorius. The assay results showed that the Siphonochilus aetiopicus and Calliandra portoricensis crude extracts, fractions and compounds displayed moderate activity against the Trypanosoma brucei but showed less activity against Leishmania mexicana. Abrus precatorius crude extract, fraction, and isolated compound exhibited only weak trypanocidal and leishmanicidal activities against both kinetoplastid parasites tested. These findings have provided evidence for the use of Siphonochilus aetiopicus and Calliandra portoricensis in traditional medicine relating to parasitic diseases.
{"title":"Antitrypanosomal and antileishmanial activity of compounds from some Nigerian plants","authors":"Samya Alenezi , Ngozichukwuka P. Igoli , Alexander I. Gray , Enimie E. Oaikhena , Ibrahim A. Alfayez , Harry P. de Koning , John O. Igoli","doi":"10.1016/j.exppara.2024.108844","DOIUrl":"10.1016/j.exppara.2024.108844","url":null,"abstract":"<div><div>Ten compounds, six extracts and five fractions obtained from three Nigerian plants were assayed for their <em>in vitro</em> antitrypanosomal and antileishmanial activities. Each plant was extacted with hexane, ethyl acetate, and methanol. Isolated compounds were characterized and identified based on their NMR chemical shifts and comparison to literature reports. The crude extracts, fractions and isolated compounds were tested against the kinetoplastid parasites: bloodstream forms of <em>Trypanosoma brucei</em> Lister 427WT and the derived multi-drug resistant clone B48, and promastigote forms of <em>Leishmania mexicana</em> cas9/T7 and the derived clone cas9ΔNT1. Column chromatography of the extracts using silica gel yielded ten compounds identified as curzerenone, epi-curzerenone, chloranthene F, isofuranodienone, 8(17)-12E-labdadiene-15, 16-dial and 15-hydroxy-8(17),12E-labdadiene-16-al from <em>Siphonochilus aetiopicus</em>, lupeol, linalolic acid and spinasterone from <em>Calliandra portoricensis,</em> and abruquinone B from <em>Abrus precatorius</em>. The assay results showed that the <em>Siphonochilus aetiopicus</em> and <em>Calliandra portoricensis</em> crude extracts, fractions and compounds displayed moderate activity against the <em>Trypanosoma brucei</em> but showed less activity against <em>Leishmania mexicana</em>. <em>Abrus precatorius</em> crude extract, fraction, and isolated compound exhibited only weak trypanocidal and leishmanicidal activities against both kinetoplastid parasites tested. These findings have provided evidence for the use of <em>Siphonochilus aetiopicus</em> and <em>Calliandra portoricensis</em> in traditional medicine relating to parasitic diseases.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108844"},"PeriodicalIF":1.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389165","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}
Developing countries continuously face challenges to get rid of amoebiasis, a protozoan disease caused by Entamoeba histolytica. Every year around 900 million people get affected by amoebiasis, among them only 10 % of people show the symptoms of the disease while 90 % of people do not show any symptoms but still, serve as carriers of the disease. Asymptomatic persons carry cysts of Entamoeba in their fecal matter, which is carried by house flies to contaminate the food and water. Entamoeba histolytica is a very successful pathogen because it has very well-developed virulence factors that function in infection to host as well as in overcoming the host's immune response. However, researchers have very little information about the clear relationship between virulence factors and the virulence of Entamoeba histolytica, through various research, researchers have been able to identify key pathogenic factors that are crucial to the pathogenesis of amoebiasis and have provided valuable insights into the development of the disease. The objective of this review is to underscore various virulence factors (Monosaccharides, Gal/GalNAc lectin, extracellular vesicles, cysteine proteases, amoeba-pores, and actin microfilament) involved in pathogenesis which may be helpful for designing of future drug or therapy.
{"title":"Role of various virulence factors involved in the pathogenesis of Entamoeba histolytica","authors":"Shubham Mathur , Sanket Kaushik , S.L. Kothari , Vijay Kumar Srivastava","doi":"10.1016/j.exppara.2024.108841","DOIUrl":"10.1016/j.exppara.2024.108841","url":null,"abstract":"<div><div>Developing countries continuously face challenges to get rid of amoebiasis, a protozoan disease caused by <em>Entamoeba histolytica.</em> Every year around 900 million people get affected by amoebiasis, among them only 10 % of people show the symptoms of the disease while 90 % of people do not show any symptoms but still, serve as carriers of the disease. Asymptomatic persons carry cysts of <em>Entamoeba</em> in their fecal matter, which is carried by house flies to contaminate the food and water. <em>Entamoeba histolytica</em> is a very successful pathogen because it has very well-developed virulence factors that function in infection to host as well as in overcoming the host's immune response. However, researchers have very little information about the clear relationship between virulence factors and the virulence of <em>Entamoeba histolytica</em>, through various research, researchers have been able to identify key pathogenic factors that are crucial to the pathogenesis of amoebiasis and have provided valuable insights into the development of the disease. The objective of this review is to underscore various virulence factors (Monosaccharides, Gal/GalNAc lectin, extracellular vesicles, cysteine proteases, amoeba-pores, and actin microfilament) involved in pathogenesis which may be helpful for designing of future drug or therapy.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108841"},"PeriodicalIF":1.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371388","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}
Pub Date : 2024-09-26DOI: 10.1016/j.exppara.2024.108840
Saleh Umair , Charlotte Bouchet , Jolyon K. Claridge , Sheralee Cleland , Warwick Grant , Jacqueline Knight
The aim of the study was to purify and characterise recombinant proteins with the potential as an anti-parasite vaccine. Full-length cDNAs encoding seryl-tRNA synthetase (srs-2) were cloned from Haemonchus contortus (HcSRS-2) and Teladorsagia circumcincta (TcSRS-2). TcSRS-2 and HcSRS-2 cDNA (1458bp) encoded proteins of 486 amino acids, each of which was present as a single band of about 55 kDa on SDS-PAGE. Multiple alignments of the protein sequences showed homology of 94% between TcSRS-2 and HcSRS-2, 76–93% with SRS-2s of eight nematodes and 68% with Mus musculus SRS-2. The predicted three-dimensional structures revealed an overall structural homology of TcSRS-2 and HcSRS-2, highly conserved binding and catalytic sites, and minor differences in the tautomerase binding site residues in other nematode SRS-2 homologues. A phylogenetic tree was constructed using helminth and mammalian SRS-2 sequences. Soluble C-terminal SRS-2 proteins were expressed in Escherichia coli strain AY2.4 and purified. Recombinant HcSRS-2 assay shows that the recombinant enzyme was active and stable. The Km and Vmax for ATP were 3.9 ± 1.0 μM and 2.7 ± 0.1 μmol min−1 mg−1 protein, respectively. Antibodies in serum and saliva from field-immune, but not nematode-naïve, sheep recognised recombinant HcSRS-2 and TcSRS-2 in enzyme-linked immunosorbent assays. Recognition of the recombinant proteins by antibodies generated by exposure of sheep to the native enzyme indicates similar antigenicity of the two proteins.
{"title":"Characterisation of seryl tRNA synthetase (srs-2) in Haemonchus contortus and Teladorsagia circumcincta","authors":"Saleh Umair , Charlotte Bouchet , Jolyon K. Claridge , Sheralee Cleland , Warwick Grant , Jacqueline Knight","doi":"10.1016/j.exppara.2024.108840","DOIUrl":"10.1016/j.exppara.2024.108840","url":null,"abstract":"<div><div>The aim of the study was to purify and characterise recombinant proteins with the potential as an anti-parasite vaccine. Full-length cDNAs encoding seryl-tRNA synthetase (<em>srs-2</em>) were cloned from <em>Haemonchus contortus</em> (<em>Hc</em>SRS-2) and <em>Teladorsagia circumcincta</em> (<em>Tc</em>SRS-2). <em>Tc</em>SRS-2 and <em>Hc</em>SRS-2 cDNA (1458bp) encoded proteins of 486 amino acids, each of which was present as a single band of about 55 kDa on SDS-PAGE. Multiple alignments of the protein sequences showed homology of 94% between <em>Tc</em>SRS-2 and <em>Hc</em>SRS-2, 76–93% with SRS-2s of eight nematodes and 68% with <em>Mus musculus</em> SRS-2. The predicted three-dimensional structures revealed an overall structural homology of <em>Tc</em>SRS-2 and <em>Hc</em>SRS-2, highly conserved binding and catalytic sites, and minor differences in the tautomerase binding site residues in other nematode SRS-2 homologues. A phylogenetic tree was constructed using helminth and mammalian SRS-2 sequences. Soluble C-terminal SRS-2 proteins were expressed in <em>Escherichia coli</em> strain AY2.4 and purified. Recombinant <em>Hc</em>SRS-2 assay shows that the recombinant enzyme was active and stable. The K<sub>m</sub> and V<sub>max</sub> for ATP were 3.9 ± 1.0 μM and 2.7 ± 0.1 μmol min<sup>−1</sup> mg<sup>−1</sup> protein, respectively. Antibodies in serum and saliva from field-immune, but not nematode-naïve, sheep recognised recombinant <em>Hc</em>SRS-2 and <em>Tc</em>SRS-2 in enzyme-linked immunosorbent assays. Recognition of the recombinant proteins by antibodies generated by exposure of sheep to the native enzyme indicates similar antigenicity of the two proteins.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108840"},"PeriodicalIF":1.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344293","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}
Pub Date : 2024-09-10DOI: 10.1016/j.exppara.2024.108830
Froylán Ibarra-Velarde , Miguel Flores-Ramos , Irene Cruz-Mendoza , Yolanda Vera-Montenegro , Alicia Hernández-Campos , Gerardo Leyva-Gómez , Tania Rojas-Campos , David Tovar-Escobar , Rafael Castillo , Rosa Arias-García , Gerardo Francisco-Márquez , Alonso Ezeta-Miranda
Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days −8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7–100%) and adult parasites (98.9–100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes.
{"title":"Fosfatriclaben: Effective dose determination and comparative efficacy assessment with closantel, triclabendazole+ivermectin, triclabendazole+albendazole in artificially infected cattle","authors":"Froylán Ibarra-Velarde , Miguel Flores-Ramos , Irene Cruz-Mendoza , Yolanda Vera-Montenegro , Alicia Hernández-Campos , Gerardo Leyva-Gómez , Tania Rojas-Campos , David Tovar-Escobar , Rafael Castillo , Rosa Arias-García , Gerardo Francisco-Márquez , Alonso Ezeta-Miranda","doi":"10.1016/j.exppara.2024.108830","DOIUrl":"10.1016/j.exppara.2024.108830","url":null,"abstract":"<div><p>Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of <em>Fasciola hepatica</em> in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 <em>F. hepatica</em> metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days −8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 <em>F.</em> hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7–100%) and adult parasites (98.9–100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult <em>F. hepatica</em> and <em>Fasciola</em> eggs; however, closantel was not sufficiently efficient against adult flukes.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108830"},"PeriodicalIF":1.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181852","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}
Pub Date : 2024-09-10DOI: 10.1016/j.exppara.2024.108839
Tatiana Guinancio de Souza , Brenda de Lucena Costa , Cleonice Andrade Holanda , Luiz Antonio Soares Romeiro , Wanderley de Souza , Marlene Benchimol
Trichomonas vaginalis is a protist parasite of the urogenital tract, responsible for human trichomoniasis, an infection sexually transmitted that affects approximately 156 million people worldwide. This pathology is more evident in females and can cause miscarriages, premature births, and infertility. The disease can also lead to a greater predisposition to HIV infection and cervical and prostate cancer. Metronidazole (MTZ) is a drug that treats human trichomoniasis. The data from studies involving human subjects are limited regarding MTZ use during pregnancy. In addition to the toxicity of the treatment, some isolates have become resistant to MTZ. Therefore, searching for new compounds active for treating trichomoniasis becomes necessary. In the present study, we report results obtained using new phospholipid analogs. Two cardanol-based compounds designated LDT117 and LDT134 were active against T. vaginalis with an IC50 of 4.58 and 10.24 μM, respectively. These compounds were not toxic to epithelial cells in culture. Scanning electron microscopy observations revealed a rounding of the cells, a shortening of the flagella, and protrusions on the surface of drug-treated cells. Transmission electron microscopy of treated cells revealed alterations in the plasma membrane with formations of blebs, protrusions, depressions, and vacuoles with myelin figures and vacuolization in the cytoplasm after incubation. Furthermore, after treatments with the compounds LDT117 and LDT134, the parasites presented a positive reaction for TUNEL, indicating death by a mechanism like apoptosis. Given the results obtained, further in vivo studies using animal experimental models are necessary to validate that these compounds are effective for treating human trichomoniasis.
{"title":"Effects of cardanol-based phospholipid analogs on Trichomonas vaginalis","authors":"Tatiana Guinancio de Souza , Brenda de Lucena Costa , Cleonice Andrade Holanda , Luiz Antonio Soares Romeiro , Wanderley de Souza , Marlene Benchimol","doi":"10.1016/j.exppara.2024.108839","DOIUrl":"10.1016/j.exppara.2024.108839","url":null,"abstract":"<div><p><em>Trichomonas vaginalis</em> is a protist parasite of the urogenital tract, responsible for human trichomoniasis, an infection sexually transmitted that affects approximately 156 million people worldwide. This pathology is more evident in females and can cause miscarriages, premature births, and infertility. The disease can also lead to a greater predisposition to HIV infection and cervical and prostate cancer. Metronidazole (MTZ) is a drug that treats human trichomoniasis. The data from studies involving human subjects are limited regarding MTZ use during pregnancy. In addition to the toxicity of the treatment, some isolates have become resistant to MTZ. Therefore, searching for new compounds active for treating trichomoniasis becomes necessary. In the present study, we report results obtained using new phospholipid analogs. Two cardanol-based compounds designated LDT117 and LDT134 were active against <em>T. vaginalis</em> with an IC<sub>50</sub> of 4.58 and 10.24 μM, respectively. These compounds were not toxic to epithelial cells in culture. Scanning electron microscopy observations revealed a rounding of the cells, a shortening of the flagella, and protrusions on the surface of drug-treated cells. Transmission electron microscopy of treated cells revealed alterations in the plasma membrane with formations of blebs, protrusions, depressions, and vacuoles with myelin figures and vacuolization in the cytoplasm after incubation. Furthermore, after treatments with the compounds LDT117 and LDT134, the parasites presented a positive reaction for TUNEL, indicating death by a mechanism like apoptosis. Given the results obtained, further <em>in vivo</em> studies using animal experimental models are necessary to validate that these compounds are effective for treating human trichomoniasis.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"266 ","pages":"Article 108839"},"PeriodicalIF":1.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169290","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}
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