Pub Date : 2025-02-06DOI: 10.1016/j.exppara.2025.108914
Larissa Chaves Freire , Scarleth Silva Costa , Ana Luiza Filizzola Tedeschi , Lucas Magno Oliveira Santos , Naianda Rezende Ribeiro , Luiza dos Reis Cruz , Vivian Tamietti Martins , Nathalia Coral Galvani , Gabriel Paulino Luiz , Maria Eduarda de Oliveira , Ricardo Andrez Machado de Ávila , Ana Maria Ravena Severino Carvalho , Henrique Santos de Freitas André , Denise Utsh Gonçalves , Eduardo Antonio Ferraz Coelho , Bruno Mendes Roatt , Daniel Menezes-Souza , Mariana Costa Duarte
In the present study, we investigated the potential use of five linear peptides as a potential antigens for the immunodiagnosis of tegumentary leishmaniasis (TL) and canine visceral leishmaniasis (CVL). We used bioinformatics approaches to identify linear B-cell epitopes in five hypothetical proteins from a Leishmania (Leishmania) infantum proteome study. To obtain the peptide sequences of each hypothetical protein, we used the GenBank and SwissProt online databases. These peptides were synthesized and tested, alone or in a cocktail, in enzyme-linked immunosorbent assays (ELISAs) against serum samples from patients with TL and from dogs infected with CVL. Our data shows that for CVL diagnosis, the best results were found with peptides 1 and 5, which showed sensitivity values of 97.30% and 94.54%, and specificity values of 93.83% (pep 1) and 91.63% (pep 5), respectively. For TL, all peptides showed higher sensitivity and specificity when compared with SLALb, with the peptide cocktail obtaining a 99.10% accuracy. This study's outcome suggests that these peptides may constitute a potential tool for a more sensitive and specific serodiagnosis of TL and CVL.
{"title":"Synthetic peptides derived from hypothetical proteins as potential antigens for the diagnosis of canine visceral leishmaniasis and tegumentary leishmaniasis","authors":"Larissa Chaves Freire , Scarleth Silva Costa , Ana Luiza Filizzola Tedeschi , Lucas Magno Oliveira Santos , Naianda Rezende Ribeiro , Luiza dos Reis Cruz , Vivian Tamietti Martins , Nathalia Coral Galvani , Gabriel Paulino Luiz , Maria Eduarda de Oliveira , Ricardo Andrez Machado de Ávila , Ana Maria Ravena Severino Carvalho , Henrique Santos de Freitas André , Denise Utsh Gonçalves , Eduardo Antonio Ferraz Coelho , Bruno Mendes Roatt , Daniel Menezes-Souza , Mariana Costa Duarte","doi":"10.1016/j.exppara.2025.108914","DOIUrl":"10.1016/j.exppara.2025.108914","url":null,"abstract":"<div><div>In the present study, we investigated the potential use of five linear peptides as a potential antigens for the immunodiagnosis of tegumentary leishmaniasis (TL) and canine visceral leishmaniasis (CVL). We used bioinformatics approaches to identify linear B-cell epitopes in five hypothetical proteins from a <em>Leishmania (Leishmania) infantum</em> proteome study. To obtain the peptide sequences of each hypothetical protein, we used the GenBank and SwissProt online databases. These peptides were synthesized and tested, alone or in a cocktail, in enzyme-linked immunosorbent assays (ELISAs) against serum samples from patients with TL and from dogs infected with CVL. Our data shows that for CVL diagnosis, the best results were found with peptides 1 and 5, which showed sensitivity values of 97.30% and 94.54%, and specificity values of 93.83% (pep 1) and 91.63% (pep 5), respectively. For TL, all peptides showed higher sensitivity and specificity when compared with SLALb, with the peptide cocktail obtaining a 99.10% accuracy. This study's outcome suggests that these peptides may constitute a potential tool for a more sensitive and specific serodiagnosis of TL and CVL.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"270 ","pages":"Article 108914"},"PeriodicalIF":1.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372904","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 : 2025-02-05DOI: 10.1016/j.exppara.2025.108913
Sagorika Panda , Rajasri Sahoo , Santi Lata Sahoo , Ranjit Manoranjan , R.C Patra
Vector-borne diseases cause increase in burden, poverty, social liability and death all over the world. Mosquitoes serve as the vector for malaria, dengue, filariasis, yellow fever and also play a major role in transmission of chikungunya and Zika virus. The development of mosquitocidal resistance and associated health problems with the use of synthetic insecticides, have paved the way to control mosquito population by using plant-based botanicals. This study was carried out to evaluate the larvicidal, pupicidal and adulticidal properties of six solvent extracts of Artemisia nilagirica (C.B.Cl) against four infectious vector mosquitoes Anopheles stephensi, Aedes aegypti, Aedes albopictus and Culex quinquefasciatus, by assessing LC50 and LC90 mortality values. Among all six leaf solvent extracts, chloroform extract had higher toxicity (LC50 = 127.27 ppm and LC90 = 544.45 ppm) against fourth instar larva of C. quinquefasciatus and aqueous extract had lowest lethal effects (LC50 = 583.33 ppm and LC90 = 927.27 ppm) against fourth instar larva of A. aegypti. Moderate results were found in n-hexane, petroleum ether, methanol and ethanol plant extracts. Phytochemical analysis by GC-MS method confirms presence of significant 12 bioactive compounds like Bi-cyclo (3.1.1) heptanes-2, 4, 6 trimethyl, 3, 7, 11, 15- Tetramethyl-1.2 hexadecan-1-ol, Thiophene, Tetrahydro-2-methyl 1,3 propane diamine and camphor, which were responsible for insecticidal activity. Altogether, current study would serve as an initial step towards replacement of synthetic insecticides to plant-based bio-pesticide against dreadful vector mosquitoes in future.
{"title":"Comparative larvicidal, pupicidal, adulticidal activity of Artemisia nilagirica (C.B. Cl) pamp extract in controlling Culex quinquefasciatus, Anopheles stephensi, Aedes aegypti and Aedes albopictus","authors":"Sagorika Panda , Rajasri Sahoo , Santi Lata Sahoo , Ranjit Manoranjan , R.C Patra","doi":"10.1016/j.exppara.2025.108913","DOIUrl":"10.1016/j.exppara.2025.108913","url":null,"abstract":"<div><div>Vector-borne diseases cause increase in burden, poverty, social liability and death all over the world. Mosquitoes serve as the vector for malaria, dengue, filariasis, yellow fever and also play a major role in transmission of chikungunya and Zika virus. The development of mosquitocidal resistance and associated health problems with the use of synthetic insecticides, have paved the way to control mosquito population by using plant-based botanicals. This study was carried out to evaluate the larvicidal, pupicidal and adulticidal properties of six solvent extracts of <em>Artemisia nilagirica</em> (C.B.Cl) against four infectious vector mosquitoes <em>Anopheles stephensi</em>, <em>Aedes aegypti</em>, <em>Aedes albopictus</em> and <em>Culex quinquefasciatus</em>, by assessing LC<sub>50</sub> and LC<sub>90</sub> mortality values. Among all six leaf solvent extracts, chloroform extract had higher toxicity (LC<sub>50</sub> = 127.27 ppm and LC<sub>90</sub> = 544.45 ppm) against fourth instar larva of <em>C. quinquefasciatus</em> and aqueous extract had lowest lethal effects (LC<sub>50</sub> = 583.33 ppm and LC<sub>90</sub> = 927.27 ppm) against fourth instar larva of <em>A. aegypti</em>. Moderate results were found in n-hexane, petroleum ether, methanol and ethanol plant extracts. Phytochemical analysis by GC-MS method confirms presence of significant 12 bioactive compounds like Bi-cyclo (3.1.1) heptanes-2, 4, 6 trimethyl, 3, 7, 11, 15- Tetramethyl-1.2 hexadecan-1-ol, Thiophene, Tetrahydro-2-methyl 1,3 propane diamine and camphor, which were responsible for insecticidal activity. Altogether, current study would serve as an initial step towards replacement of synthetic insecticides to plant-based bio-pesticide against dreadful vector mosquitoes in future.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108913"},"PeriodicalIF":1.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374060","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108898
Priyanka H. Mazire, Snehal Shingade, Amit Roy
Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment. Therefore, it is crucial to discover and develop newer potent antileishmanial agents for successful eradication of the disease. Our previous report, for the first time showed the leishminicidal effect of amprenavir (APV) mediated by inhibition of L.donovani Topoisomerase I (LdTopILS). So, we intended to demonstrate the effect of APV in combination with ritonavir (RTV). The present study revealed that the complete catalytic inhibition of LdTopILS by APV (10 μM) in combination with RTV (5 μM), compare to APV (20 μM) as previously reported (Roy et al., 2021). Moreover, APV (5 μM) in combination with RTV (4 μM) exhibited promastigote inhibition with IC50 values of 2.4 ± 0.6 μM at 12 h and 1.6 ± 0.7 μM at 24 h, respectively. The study was extended in animal model where the in vivo antileishmanial efficacy of APV-RTV in BALB/c mice demonstrated that treatment of APV in combination with RTV led to significant splenic and hepatic protection as compared to single dose of APV. Moreover, the antileishmanial activity of APV in combination with RTV was exerted via inhibition of LdTopILS at much lower concentration of APV and this inhibition of the enzyme induced programmed cell death in Leishmania parasites by generating oxidative stress within the cells. From the in vitro, ex vivo and in vivo studies, it was indicated that lower dose of APV in combination with RTV elevated the effective killing of the parasites as compared to the single higher dose of APV. Thus, the current study highlights repurposing of available protease inhibitors in combination, which might be exploited further for the therapeutic development against VL as well as HIV-VL co-infection.
{"title":"Ritonavir enhances the efficacy of amprenavir: A promising combination therapy by targeting Leishmania DNA topoisomerase I for treatment of visceral leishmaniasis","authors":"Priyanka H. Mazire, Snehal Shingade, Amit Roy","doi":"10.1016/j.exppara.2025.108898","DOIUrl":"10.1016/j.exppara.2025.108898","url":null,"abstract":"<div><div>Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment. Therefore, it is crucial to discover and develop newer potent antileishmanial agents for successful eradication of the disease. Our previous report, for the first time showed the leishminicidal effect of amprenavir (APV) mediated by inhibition of <em>L.donovani</em> Topoisomerase I (LdTopILS). So, we intended to demonstrate the effect of APV in combination with ritonavir (RTV). The present study revealed that the complete catalytic inhibition of LdTopILS by APV (10 μM) in combination with RTV (5 μM), compare to APV (20 μM) as previously reported (Roy et al., 2021). Moreover, APV (5 μM) in combination with RTV (4 μM) exhibited promastigote inhibition with IC<sub>50</sub> values of 2.4 ± 0.6 μM at 12 h and 1.6 ± 0.7 μM at 24 h, respectively. The study was extended in animal model where the <em>in vivo</em> antileishmanial efficacy of APV-RTV in BALB/c mice demonstrated that treatment of APV in combination with RTV led to significant splenic and hepatic protection as compared to single dose of APV. Moreover, the antileishmanial activity of APV in combination with RTV was exerted via inhibition of LdTopILS at much lower concentration of APV and this inhibition of the enzyme induced programmed cell death in <em>Leishmania</em> parasites by generating oxidative stress within the cells. From the <em>in vitro, ex vivo</em> and <em>in vivo</em> studies, it was indicated that lower dose of APV in combination with RTV elevated the effective killing of the parasites as compared to the single higher dose of APV. Thus, the current study highlights repurposing of available protease inhibitors in combination, which might be exploited further for the therapeutic development against VL as well as HIV-VL co-infection.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108898"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970292","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 : 2025-02-01DOI: 10.1016/j.exppara.2024.108888
Ángel E. Lobo-Rojas , María A. Delgado-Chacón , Edward A. Valera-Vera , Marirene Chacón-Arnaude , Mary Carmen Pérez-Aguilar , Rocío Rondón-Mercado , Ender Quintero-Troconis , Wilfredo Quiñones , Juan L. Concepción , Ana J. Cáceres
In Leishmania, the nucleotide-sugar UDP-galactose can be synthesized by a salvage pathway, the Isselbacher route, involving phosphorylation of galactose and the action of UDP-sugar pyrophosphorylase. The first enzyme of the pathway, galactokinase, has yet to be studied in this parasite. Here, we report a molecular and biochemical characterization of this enzyme in Leishmania mexicana. We showed that recombinant galactokinase (LmxGALK) phosphorylates galactose in the presence of ATP with Km values of 0.077 mM for galactose and 0.017 mM for ATP. We proved by immunodetection that GALK is expressed in promastigotes and amastigotes of L. mexicana, L. braziliensis and L. infantum. In agreement with the presence of a type 1 peroxisome-targeting signal sequence present at the C-terminus of LmxGALK, the protein is localized mostly within glycosomes as shown by selective membrane permeabilization with digitonin, differential centrifugation, and immunofluorescence. Indeed, LmxGALK enzymatic activity was measured in the fractions corresponding to the homogenate and glycosomes, proving that it is active in promastigotes. In addition, it was shown that galactose cannot serve as an important carbon source for sustaining parasite growth, as cultures of promastigotes from three Leishmania species in LIT medium containing either no sugar or supplemented with D-galactose (20 mM) grew to lower density compared to these cultured with D-glucose (20 mM). These results suggest that D-galactose is mainly used for UDP-galactose synthesis by the salvage route, functioning when glucose is depleted from the medium, similar to the conditions promastigotes experience in the gut of the insect vector during its life cycle.
{"title":"Galactokinase and galactose metabolism in Leishmania spp.","authors":"Ángel E. Lobo-Rojas , María A. Delgado-Chacón , Edward A. Valera-Vera , Marirene Chacón-Arnaude , Mary Carmen Pérez-Aguilar , Rocío Rondón-Mercado , Ender Quintero-Troconis , Wilfredo Quiñones , Juan L. Concepción , Ana J. Cáceres","doi":"10.1016/j.exppara.2024.108888","DOIUrl":"10.1016/j.exppara.2024.108888","url":null,"abstract":"<div><div>In <em>Leishmania</em>, the nucleotide-sugar UDP-galactose can be synthesized by a salvage pathway, the Isselbacher route, involving phosphorylation of galactose and the action of UDP-sugar pyrophosphorylase. The first enzyme of the pathway, galactokinase, has yet to be studied in this parasite. Here, we report a molecular and biochemical characterization of this enzyme in <em>Leishmania mexicana</em>. We showed that recombinant galactokinase (<em>Lmx</em>GALK) phosphorylates galactose in the presence of ATP with <em>K</em><sub>m</sub> values of 0.077 mM for galactose and 0.017 mM for ATP. We proved by immunodetection that GALK is expressed in promastigotes and amastigotes of <em>L</em>. <em>mexicana</em>, <em>L</em>. <em>braziliensis</em> and <em>L. infantum</em>. In agreement with the presence of a type 1 peroxisome-targeting signal sequence present at the C-terminus of <em>Lmx</em>GALK, the protein is localized mostly within glycosomes as shown by selective membrane permeabilization with digitonin, differential centrifugation, and immunofluorescence. Indeed, <em>Lmx</em>GALK enzymatic activity was measured in the fractions corresponding to the homogenate and glycosomes, proving that it is active in promastigotes. In addition, it was shown that galactose cannot serve as an important carbon source for sustaining parasite growth, as cultures of promastigotes from three <em>Leishmania</em> species in LIT medium containing either no sugar or supplemented with D-galactose (20 mM) grew to lower density compared to these cultured with D-glucose (20 mM). These results suggest that D-galactose is mainly used for UDP-galactose synthesis by the salvage route, functioning when glucose is depleted from the medium, similar to the conditions promastigotes experience in the gut of the insect vector during its life cycle.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108888"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913889","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 : 2025-02-01DOI: 10.1016/j.exppara.2024.108882
Aqib, Zaki Anwar Siddiqui
Effect of Meloidogyne incognita and Pseudomonas syringae pv. aptata (Psa) was observed singly, together and pre and post inoculations in 4 soil types on plant growth parameters, chlorophyll, carotenoid and proline contents of beetroot (Beta vulgaris L.). Plant growth, chlorophyll and carotenoid contents were greater in loam soil followed by 20% fly ash soil, 10% fly ash plus 10% sand amended soil and least in 20 % sand mix soil. However, proline contents were high in 20% sand mix soil and least in loam soil. Plant growth (root dry weight), chlorophyll and carotenoid contents were reduced in plants inoculated with any test pathogen while proline contents were increased in plants inoculated with pathogens under study. Inoculation of both pathogens together caused a greater reduction of plant growth, chlorophyll and carotenoid contents than their individual inoculation. Inoculation of M. incognita 20 days prior to Psa resulted in greatest reduction in plant growth, chlorophyll and carotenoid and maximum proline contents. Inoculation of Psa with M. incognita reduced galling and nematode multiplication while prior inoculation of Psa caused maximum reduction in galling and nematode multiplication. Galling and nematode multiplication was high in 20% sand mix soil followed by loam soil and least in 20% fly ash amended soil. Bacterial leaf spot indices by Psa was 3 when alone. Disease indices were 5 when Psa was inoculated with M. incognita. Prior inoculation of M. incognita predisposed beetroots to Psa and aggravates the disease. Influence of M. incognita, Psa and their interactions in different soil types on various studied parameters in diseased plants was demonstrated by Principal component analysis.
{"title":"Interaction of Meloidogyne incognita and Pseudomonas syringae pv. aptata in different types of soil on plant growth, photosynthetic pigments and proline contents of beetroot (Beta vulgaris L.)","authors":"Aqib, Zaki Anwar Siddiqui","doi":"10.1016/j.exppara.2024.108882","DOIUrl":"10.1016/j.exppara.2024.108882","url":null,"abstract":"<div><div>Effect of <em>Meloidogyne incognita</em> and <em>Pseudomonas syringae</em> pv. <em>aptata</em> (<em>Psa</em>) was observed singly, together and pre and post inoculations in 4 soil types on plant growth parameters, chlorophyll, carotenoid and proline contents of beetroot (<em>Beta vulgaris</em> L.). Plant growth, chlorophyll and carotenoid contents were greater in loam soil followed by 20% fly ash soil, 10% fly ash plus 10% sand amended soil and least in 20 % sand mix soil. However, proline contents were high in 20% sand mix soil and least in loam soil. Plant growth (root dry weight), chlorophyll and carotenoid contents were reduced in plants inoculated with any test pathogen while proline contents were increased in plants inoculated with pathogens under study. Inoculation of both pathogens together caused a greater reduction of plant growth, chlorophyll and carotenoid contents than their individual inoculation. Inoculation of <em>M. incognita</em> 20 days prior to <em>Psa</em> resulted in greatest reduction in plant growth, chlorophyll and carotenoid and maximum proline contents<em>.</em> Inoculation of <em>Psa</em> with <em>M. incognita</em> reduced galling and nematode multiplication while prior inoculation of <em>Psa</em> caused maximum reduction in galling and nematode multiplication. Galling and nematode multiplication was high in 20% sand mix soil followed by loam soil and least in 20% fly ash amended soil. Bacterial leaf spot indices by <em>Psa</em> was 3 when alone. Disease indices were 5 when <em>Psa</em> was inoculated with <em>M. incognita</em>. Prior inoculation of <em>M. incognita</em> predisposed beetroots to <em>Psa</em> and aggravates the disease. Influence of <em>M. incognita</em>, <em>Psa</em> and their interactions in different soil types on various studied parameters in diseased plants was demonstrated by Principal component analysis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108882"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871890","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108900
Keon-Woong Yoon , Gi-Deok Eom , Jie Mao , Min-Ju Kim , Su In Heo , Hae-Ji Kang , Ki Back Chu , Eun-Kyung Moon , Fu-Shi Quan
Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism Toxoplasma gondii. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the T. gondii rhoptry protein 4 (ROP4) antigen and evaluated its efficacy in a murine model. Intranasal vaccination with ROP4-rVacvs induced parasite-specific serum antibody responses as early as 3 weeks post-immunization, with subsequent immunizations elevating antibody responses to a greater extent. When challenged with T. gondii ME49 strain, significantly enhanced levels of mucosal IgA antibodies were detected in the intestines of immunized mice. Additionally, ROP4-rVacv immunization ensured that T cells and germinal center B cell populations were retained at high levels. These immune responses mitigated the severity of neuroinflammation, reduced tissue cyst formation, and ensured the survival of immunized mice. Our findings indicate that ROP4-rVacv could be a promising toxoplasmosis vaccine candidate.
{"title":"Protection induced by recombinant vaccinia virus targeting the ROP4 of Toxoplasma gondii in mice","authors":"Keon-Woong Yoon , Gi-Deok Eom , Jie Mao , Min-Ju Kim , Su In Heo , Hae-Ji Kang , Ki Back Chu , Eun-Kyung Moon , Fu-Shi Quan","doi":"10.1016/j.exppara.2025.108900","DOIUrl":"10.1016/j.exppara.2025.108900","url":null,"abstract":"<div><div>Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism <em>Toxoplasma gondii</em>. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the <em>T. gondii</em> rhoptry protein 4 (ROP4) antigen and evaluated its efficacy in a murine model. Intranasal vaccination with ROP4-rVacvs induced parasite-specific serum antibody responses as early as 3 weeks post-immunization, with subsequent immunizations elevating antibody responses to a greater extent. When challenged with <em>T. gondii</em> ME49 strain, significantly enhanced levels of mucosal IgA antibodies were detected in the intestines of immunized mice. Additionally, ROP4-rVacv immunization ensured that T cells and germinal center B cell populations were retained at high levels. These immune responses mitigated the severity of neuroinflammation, reduced tissue cyst formation, and ensured the survival of immunized mice. Our findings indicate that ROP4-rVacv could be a promising toxoplasmosis vaccine candidate.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108900"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970291","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108897
Everton Allan Ferreira , Igor Moreira Campos , Rayssa A. Cajas , Danilo de Souza Costa , Lara Soares Aleixo de Carvalho , Paula Fernandes da Costa Franklin , Nathália de Paula D. de Nigro , Priscila de Faria Pinto , PriscilaV.S.Z. Capriles , Josué de Moraes , Ademar A. da Silva Filho
Schistosomiasis stands as one of the most significant parasitic diseases on a global scale, with approximately 250 million infections worldwide. It is imperative to address this pressing issue by developing new antischistosomal drugs. Chalcones have emerged as a promising class of natural compounds, demonstrating noteworthy effects observed in vitro experiments with Schistosoma mansoni, and demonstrating the ability to inhibit SmNTPDases and apyrase from potatoes. In this study, we focused on uvangoletin, a naturally occurring dihydrochalcone from Piper aduncum. We isolated uvangoletin from P. aduncum fruits and conducted in vivo experiments to evaluate the efficacy of uvangoletin against adult Schistosoma parasites. Furthermore, we explored the inhibitory effects of uvangoletin on potato apyrase and employed molecular docking analyses to investigate its interactions with apyrase from potato and the two isoforms SmNTPDase 1 and 2 through in silico studies. Uvangoletin (400 mg/kg, p. o.), exhibited significant in vivo antiparasitic effects against adult S. mansoni, leading to a decrease of 53.7% in worm burden and 54.3% in egg production. The treatment also reduced hepatomegaly and splenomegaly. In silico investigations and ADMET studies indicated that uvangoletin possesses favorable drug-like properties and may interact with key residues involved in apyrase and SmNTPDases activities. Furthermore, uvangoletin demonstrated a substantial reduction in potato apyrase activity. These results suggest the potential for exploring other dihydrochalcones as promising candidates for antischistosomal agents.
{"title":"In vivo efficacy of uvangoletin from Piper aduncum (Piperaceae) against Schistosoma mansoni and in silico studies targeting SmNTPDases","authors":"Everton Allan Ferreira , Igor Moreira Campos , Rayssa A. Cajas , Danilo de Souza Costa , Lara Soares Aleixo de Carvalho , Paula Fernandes da Costa Franklin , Nathália de Paula D. de Nigro , Priscila de Faria Pinto , PriscilaV.S.Z. Capriles , Josué de Moraes , Ademar A. da Silva Filho","doi":"10.1016/j.exppara.2025.108897","DOIUrl":"10.1016/j.exppara.2025.108897","url":null,"abstract":"<div><div>Schistosomiasis stands as one of the most significant parasitic diseases on a global scale, with approximately 250 million infections worldwide. It is imperative to address this pressing issue by developing new antischistosomal drugs. Chalcones have emerged as a promising class of natural compounds, demonstrating noteworthy effects observed in <em>vitro</em> experiments with <em>Schistosoma mansoni</em>, and demonstrating the ability to inhibit SmNTPDases and apyrase from potatoes. In this study, we focused on uvangoletin, a naturally occurring dihydrochalcone from <em>Piper aduncum</em>. We isolated uvangoletin from <em>P. aduncum</em> fruits and conducted <em>in vivo</em> experiments to evaluate the efficacy of uvangoletin against adult <em>Schistosoma</em> parasites. Furthermore, we explored the inhibitory effects of uvangoletin on potato apyrase and employed molecular docking analyses to investigate its interactions with apyrase from potato and the two isoforms SmNTPDase 1 and 2 through <em>in silico</em> studies. Uvangoletin (400 mg/kg, p. o.), exhibited significant <em>in vivo</em> antiparasitic effects against adult <em>S. mansoni</em>, leading to a decrease of 53.7% in worm burden and 54.3% in egg production. The treatment also reduced hepatomegaly and splenomegaly. <em>In silico</em> investigations and ADMET studies indicated that uvangoletin possesses favorable drug-like properties and may interact with key residues involved in apyrase and SmNTPDases activities. Furthermore, uvangoletin demonstrated a substantial reduction in potato apyrase activity. These results suggest the potential for exploring other dihydrochalcones as promising candidates for antischistosomal agents.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108897"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970247","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 : 2025-02-01DOI: 10.1016/j.exppara.2024.108881
Ingrid Lins Raquel de Jesus , Fernando Rocha Miranda , Thais Paes Ferreira , Alice Ortega do Nascimento , Karen Kuhfuss da Silva de Lima , Bárbara Rauta de Avelar , Diefrey Ribeiro Campos , Yara Peluso Cid
The flea Ctenocephalides felis felis and the tick Rhipicephalus sanguineus are ectoparasites of great importance in veterinary medicine that can affect pets, also impacting the lives of owners due to the possible transmission of zoonoses. Due to the negative impact on animals, owners and the environment, synthetic chemicals are being replaced by natural alternatives. Eugenol and carvacrol stand out as bioactive substances with potential antiparasitic activity. The aim of the present study was to develop and characterize physicochemically spray and spot-on formulations containing bioactives alone and in combination and to evaluate their ectoparasiticidal activity through in vitro bioassays of the knockdown effect and residual efficacy against adult fleas and ticks. Regarding flea knockdown, spot-on formulations achieved maximum mortality in a shorter period than spray formulations, 2 h for carvacrol plus eugenol (SCE) and 4 h for carvacrol (SC) and eugenol (SE) alone, compared to 15, 30 and 45 min for the spot-on formulations of carvacrol (PC), both substances together (PCE) and eugenol alone (PE), respectively. For tick control, the formulations required longer exposure times than for fleas, so that 100% control took 6 h for PCE, followed by 12 h for SCE and PE, and 24 h for PC, SC and PE. Regarding residual efficacy against fleas, the spray and spot-on formulations remained active for approximately 90 and 45 days, respectively. In general, formulations containing associated bioactives had a faster knockdown effect than formulations with only one in their composition, indicating a synergistic effect of the two bioactive substances against fleas and ticks.
{"title":"Bioactive-based spray and spot-on formulations: Development, characterization and in vitro efficacy against fleas and ticks","authors":"Ingrid Lins Raquel de Jesus , Fernando Rocha Miranda , Thais Paes Ferreira , Alice Ortega do Nascimento , Karen Kuhfuss da Silva de Lima , Bárbara Rauta de Avelar , Diefrey Ribeiro Campos , Yara Peluso Cid","doi":"10.1016/j.exppara.2024.108881","DOIUrl":"10.1016/j.exppara.2024.108881","url":null,"abstract":"<div><div>The flea <em>Ctenocephalides felis felis</em> and the tick <em>Rhipicephalus sanguineus</em> are ectoparasites of great importance in veterinary medicine that can affect pets, also impacting the lives of owners due to the possible transmission of zoonoses. Due to the negative impact on animals, owners and the environment, synthetic chemicals are being replaced by natural alternatives. Eugenol and carvacrol stand out as bioactive substances with potential antiparasitic activity. The aim of the present study was to develop and characterize physicochemically spray and spot-on formulations containing bioactives alone and in combination and to evaluate their ectoparasiticidal activity through <em>in vitro</em> bioassays of the knockdown effect and residual efficacy against adult fleas and ticks. Regarding flea knockdown, spot-on formulations achieved maximum mortality in a shorter period than spray formulations, 2 h for carvacrol plus eugenol (SCE) and 4 h for carvacrol (SC) and eugenol (SE) alone, compared to 15, 30 and 45 min for the spot-on formulations of carvacrol (PC), both substances together (PCE) and eugenol alone (PE), respectively. For tick control, the formulations required longer exposure times than for fleas, so that 100% control took 6 h for PCE, followed by 12 h for SCE and PE, and 24 h for PC, SC and PE. Regarding residual efficacy against fleas, the spray and spot-on formulations remained active for approximately 90 and 45 days, respectively. In general, formulations containing associated bioactives had a faster knockdown effect than formulations with only one in their composition, indicating a synergistic effect of the two bioactive substances against fleas and ticks.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108881"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871766","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 : 2025-02-01DOI: 10.1016/j.exppara.2024.108887
Gulnara N. Karimbayova , Eldar K. Gasimov , Farid R. Mahmudov , Fuad H. Rzayev , Rovshan Khalilov , Aziz Eftekhari , Ayşe Baran
A light and electron microscopic study of skin biopsies taken from 9 patients with ulcerative leishmaniasis of both sexes aged from 14 to 26 years in the territory of the Republic of Azerbaijan was carried out. Based on clinical, morphological and electron microscopic parameters, all patients were diagnosed with ulcerative cutaneous anthroponotic leishmaniasis (Leishmania (L.) tropica). Stained and unstained ultrathin (50–70 nm) sections were viewed and photographed using a JEM-1400 transmission electron microscope at an accelerating voltage of 80–120 kV. Analysis of data from light and electron microscopic studies at the ultrastructural level made it possible to describe the structure and identify the morphometric parameters of the amastigote form of the intracellular parasite. Besides, it was found that the distance between the plasmalemmas of the parasitophorous vacuoles and the parasite L. (L.) tropica is only 1 nm. This facilitates the passage of the necessary nutrients for the survival of this parasite. One of the important factors in the chronic course and relapse of leishmaniasis caused by L.(L.) tropica is the penetration of the amastigote stage into the cytoplasm along with macrophages, and also into fibroblasts with low phagocytic activity. Pathological changes (deformed nucleus, damage to plasmalemma, focal destruction of the cytoplasm structures, vacuolization, etc.) in the parasite L. (L.) tropica, localized in macrophages, were identified and described.
{"title":"Ultrastructural characteristics of leishmania (L.)tropica (Wright, 1903) and cell-parasite relationships in cutaneous leishmaniasis. Light and electron microscopic study","authors":"Gulnara N. Karimbayova , Eldar K. Gasimov , Farid R. Mahmudov , Fuad H. Rzayev , Rovshan Khalilov , Aziz Eftekhari , Ayşe Baran","doi":"10.1016/j.exppara.2024.108887","DOIUrl":"10.1016/j.exppara.2024.108887","url":null,"abstract":"<div><div>A light and electron microscopic study of skin biopsies taken from 9 patients with ulcerative leishmaniasis of both sexes aged from 14 to 26 years in the territory of the Republic of Azerbaijan was carried out. Based on clinical, morphological and electron microscopic parameters, all patients were diagnosed with ulcerative cutaneous anthroponotic leishmaniasis (<em>Leishmania</em> (<em>L.</em>) <em>tropica</em>). Stained and unstained ultrathin (50–70 nm) sections were viewed and photographed using a JEM-1400 transmission electron microscope at an accelerating voltage of 80–120 kV. Analysis of data from light and electron microscopic studies at the ultrastructural level made it possible to describe the structure and identify the morphometric parameters of the amastigote form of the intracellular parasite. Besides, it was found that the distance between the plasmalemmas of the parasitophorous vacuoles and the parasite <em>L. (L.) tropica</em> is only 1 nm. This facilitates the passage of the necessary nutrients for the survival of this parasite. One of the important factors in the chronic course and relapse of leishmaniasis caused by <em>L.(L.) tropica</em> is the penetration of the amastigote stage into the cytoplasm along with macrophages, and also into fibroblasts with low phagocytic activity. Pathological changes (deformed nucleus, damage to plasmalemma, focal destruction of the cytoplasm structures, vacuolization, etc.) in the parasite <em>L. (L.) tropica,</em> localized in macrophages, were identified and described.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108887"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913894","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108896
Marília A. Machado , Debora A. Borges , Diefrey R. Campos , Natália L. Lopes , Fabio B. Scott , Julio I. Fernandes
The aim of this study was to evaluate the efficacy of a single 20 mg/kg dose of lotilaner for treating rabbits with concomitant infection by P. ovis and L. gibbus. Fourteen rabbits with diagnoses of otitis and fur infection, caused respectively by P. ovis and L. gibbus, were included. Samples of otic crust were collected with tweezers, weighed and examined microscopically to identify ectoparasites, which were counted to determine the number of mites per gram of crust. Hair samples were collected from three areas of 1 cm2 in different regions of the body, for examination under a stereomicroscope to determine occurrences of the mite L. gibbus. The animals in the treated group received a single oral dose of 20 mg/kg of lotilaner and were evaluated on days 0, +3, +7, +14, +21, +28 and + 35. Parasitological efficacy of 100% for controlling P. ovis was observed after seven days. Total clinical remission was reached 14 days after treatment. For L. gibbus, parasitological cure was obtained seven days after treatment. We concluded that a single dose of lotilaner was effective for controlling P. ovis and L. gibbus, leading to parasitological control and clinical improvement of the animals.
{"title":"Efficacy of lotilaner for treating rabbits naturally infested by Psoroptes ovis and Leporacarus gibbus, in Rio de Janeiro, Brazil","authors":"Marília A. Machado , Debora A. Borges , Diefrey R. Campos , Natália L. Lopes , Fabio B. Scott , Julio I. Fernandes","doi":"10.1016/j.exppara.2025.108896","DOIUrl":"10.1016/j.exppara.2025.108896","url":null,"abstract":"<div><div>The aim of this study was to evaluate the efficacy of a single 20 mg/kg dose of lotilaner for treating rabbits with concomitant infection by <em>P. ovis</em> and <em>L. gibbus</em>. Fourteen rabbits with diagnoses of otitis and fur infection, caused respectively by <em>P. ovis</em> and <em>L. gibbus</em>, were included. Samples of otic crust were collected with tweezers, weighed and examined microscopically to identify ectoparasites, which were counted to determine the number of mites per gram of crust. Hair samples were collected from three areas of 1 cm<sup>2</sup> in different regions of the body, for examination under a stereomicroscope to determine occurrences of the mite <em>L. gibbus</em>. The animals in the treated group received a single oral dose of 20 mg/kg of lotilaner and were evaluated on days 0, +3, +7, +14, +21, +28 and + 35. Parasitological efficacy of 100% for controlling <em>P. ovis</em> was observed after seven days. Total clinical remission was reached 14 days after treatment. For L. <em>gibbus</em>, parasitological cure was obtained seven days after treatment. We concluded that a single dose of lotilaner was effective for controlling <em>P. ovis</em> and <em>L. gibbus,</em> leading to parasitological control and clinical improvement of the animals.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108896"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947102","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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