RESUMEN
Ticks are notorious blood-sucking ectoparasites that affect both humans and animals. They serve as a unique vector of various deadly diseases. Here, we have shown the roles of the receptor for advanced glycation end products (RAGE) during repeated infestations by the tick Haemaphysalis longicornis using RAGE-/- mice. In primary infestation, a large blood pool developed, which was flooded with numerous RBCs, especially during the rapid feeding phase of the tick both in wild-type (wt) and RAGE-/- mice. Very few inflammatory cells were detected around the zones of haemorrhage in the primary infestations. However, the number of inflammatory cells gradually increased in the subsequent tick infestations, and during the third infestations, the number of inflammatory cells reached to the highest level (350.3 ± 16.8 cells/focus). The site of attachment was totally occupied by the inflammatory cells in wt mice, whereas very few cells were detected at the ticks' biting sites in RAGE-/- mice. RAGE was highly expressed during the third infestation in wt mice. In the third infestation, infiltration of CD44+ lymphocytes, eosinophils and expression of S100A8 and S100B significantly increased at the biting sites of ticks in wt, but not in RAGE-/- mice. In addition, peripheral eosinophil counts significantly increased in wt but not in RAGE-/- mice. Taken together, our study revealed that RAGE-mediated inflammation and eosinophils played crucial roles in the tick-induced inflammatory reactions.
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Inflamación , Ixodidae , Ratones Noqueados , Receptor para Productos Finales de Glicación Avanzada , Infestaciones por Garrapatas , Animales , Ixodidae/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Ratones , Infestaciones por Garrapatas/inmunología , Ratones Endogámicos C57BL , Femenino , Conducta Alimentaria , Haemaphysalis longicornisRESUMEN
The emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni), make the development of new antischistosomal drugs urgent. The parasite's mitochondrion is an attractive target for drug development, because this organelle is essential for survival throughout the parasite's life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercaria motility that have been reported to affect mitochondrion-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against the motility of schistosomula (in vitro) and adults (ex vivo). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% of that obtained in the vehicle control. Notably, ascofuranone showed the highest activity, with a 98% reduction of the worm burden, suggesting the potential for the development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and nonmitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are a feasible target for drug development.
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Preparaciones Farmacéuticas , Esquistosomiasis mansoni , Esquistosomicidas , Animales , Ratones , Mitocondrias , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/prevención & control , Esquistosomicidas/uso terapéuticoRESUMEN
Thus far, Entamoeba species have been classified based on morphology such as the number of nuclei in mature cysts and their hosts. Using recently developed molecular tools, ruminant Entamoeba spp. are currently classified into four species/genotypes: E. bovis and Entamoeba ribosomal lineages (RL) 1, 2, and 4. However, the distribution or pathogenicity of ruminant Entamoeba has not been well documented. In the present study, we examined a total of 25 fecal and seven environmental samples collected from six farms in Japan from 2016 to 2017 by the floatation method and PCR and sequencing analyses. Consequently, we detected Entamoeba cysts in 18 of 25 cattle samples and four of the seven environmental samples, including soil and drinking water, by microscopic examinations. In sequential examinations, Entamoeba-positive cattle were found to shed cysts without any clinical symptoms for more than 8 months. By PCR for molecular identification, isolates in ten cattle and one soil sample were successfully sequenced and formed a cluster of E. bovis, which was separated from those of other Entamoeba species/genotypes such as RL1-4 in phylogenetic analysis. To our knowledge, this is the first report about E. bovis in Japan, and our results may implicate that E. bovis is not pathogenic.
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Enfermedades de los Bovinos/parasitología , Entamoeba/aislamiento & purificación , Entamebiasis/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Entamoeba/genética , Entamoeba/patogenicidad , Entamebiasis/epidemiología , Entamebiasis/parasitología , Heces/parasitología , Genotipo , Japón/epidemiología , FilogeniaRESUMEN
The previous release of our Full-parasites database (http://fullmal.hgc.jp/) brought enhanced functionality, an expanded full-length cDNA content, and new RNA-Seq datasets from several important apicomplexan parasites. The 2015 update witnesses the major shift in the databases content with focus on diverse transcriptomes of the apicomplexan parasites. The content of the database was substantially enriched with transcriptome information for new apicomplexan parasites. The latest version covers a total of 17 species, with addition of our newly generated RNA-Seq data of a total of 909,150,388 tags. Moreover, we have generated and included two novel and unique datasets, which represent diverse nature of transcriptomes in individual parasites in vivo and in vitro. One is the data collected from 116 Indonesian patients infected with Plasmodium falciparum. The other is a series of transcriptome data collected from a total of 38 single cells of P. falciparum cultured in vitro. We believe that with the recent advances our database becomes an even better resource and a unique platform in the analysis of apicomplexan parasites and their interaction with their hosts. To adequately reflect the recent modifications and the current content we have changed the database name to DB-AT--DataBase of Apicomplexa Transcriptomes.
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Apicomplexa/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Humanos , Internet , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Análisis de Secuencia de ARNRESUMEN
In the poultry industry, Eimeria spp. is one of the important pathogens which cause significant economic losses. We have previously generated a chicken monoclonal antibody (mAb), 6D-12-G10, with specificity for an antigen located in the apical cytoskeleton of Eimeria acervulina and with cross-reactive among Apicomplexan parasites, including other Eimeria spp., Toxoplasma, Neospora, and Cryptosporidium spp. Furthermore, the protein of Cryptosporidium parvum recognized by the 6D-12-G10 has been identified as elongation factor-1α (EF-1α). In the present study, to identify the target molecule of E. acervulina by the mAb, we performed two-dimensional Western blotting analysis. Finally, we found two positive molecules which are identified as EF-1α and a related protein. Our previous finding using C. parvum and the results in this study suggest that EF-1α could be associated with the invasion facilitated by the cytoskeleton at the apical region of zoites.
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Antígenos de Protozoos/inmunología , Pollos/parasitología , Coccidiosis/veterinaria , Eimeria/inmunología , Factor 1 de Elongación Peptídica/metabolismo , Enfermedades de las Aves de Corral/parasitología , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antiprotozoarios/inmunología , Western Blotting/veterinaria , Coccidiosis/parasitología , Reacciones Cruzadas , Cryptosporidium parvum/inmunología , Cryptosporidium parvum/aislamiento & purificación , Eimeria/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/veterinaria , Neospora/inmunología , Neospora/aislamiento & purificación , Esporozoítos , Toxoplasma/inmunología , Toxoplasma/aislamiento & purificaciónRESUMEN
Mucin is a major component of mucus on gastrointestinal mucosa. Mucin alteration in the host is considered to be the principal event for expulsion of intestinal helminths. However, it is unclear what mucin alterations are induced by various helminth infections. In this study, the alterations of mouse small intestinal mucin after infection with two nematodes, Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which parasitize the jejunal epithelium, and a cestode, Vampirolepis nana, which parasitizes the ileal epithelium, were examined biochemically and histologically using two anti-mucin monoclonal antibodies (mAbs), HCM31 and PGM34, which recognize Sd(a) antigen, NeuAcα2-3(GalNAcß1-4)Galß1-4GlcNAcß-, and sulphated H type 2 antigen, Fucα1-2Galß1-4GlcNAc(6SO3H)ß-, respectively. The goblet cell mucins that reacted with HCM31 increased conspicuously on the jejunal mucosa concurrently with expulsion of N. brasiliensis. Increased levels of HCM31-reactive mucins were observed in the jejunal mucosa after H. polygyrus infection, despite the ongoing parasitism. Goblet cell mucins that reacted with PGM34 increased on the ileal mucosa during V. nana parasitism. Small intestinal goblet cells reacting with the two mAbs were not observed in non-infected mice, although sialomucins and sulfomucins were abundantly present. Additionally, the number of ileal goblet cells that reacted with the two mAbs was increased at the time of expulsion of heterophyid trematode. These results indicate that the type of specific acidic mucins expressed after infection varies among species of intestinal helminth, and, furthermore, that the relationship with worm expulsion is also different.
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Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Mucinas/metabolismo , Nematospiroides dubius/fisiología , Nippostrongylus/fisiología , Sialomucinas/metabolismo , Infecciones por Strongylida/metabolismo , Infecciones por Strongylida/parasitología , Animales , Células Caliciformes/metabolismo , Células Caliciformes/parasitología , Células Caliciformes/patología , Humanos , Mucosa Intestinal/parasitología , Mucosa Intestinal/patología , Yeyuno/parasitología , Yeyuno/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Mucinas/genética , Sialomucinas/genética , Infecciones por Strongylida/genética , Infecciones por Strongylida/patologíaRESUMEN
Infections by gastrointestinal parasites are found in a variety of animals worldwide. For the diagnosis of such infections, the flotation method is commonly used to detect parasitic microorganisms, such as oocysts or eggs, in feces. Instead of adding a flotation solution after the final centrifugation step and using a cover slip to collect the parasites, the method using a wire loop for the recovery of the organisms has been reported as one of alternative methods. However, the recovery rates of microorganisms from the flotation method have not been analysed. In the present study, the utility of a flotation method with the use of a wire loop of 8 mm in diameter (the loop method) was evaluated using different numbers of E. tenella oocysts and Heterakis gallinarum eggs, and chicken fecal samples collected at the farms. Consequently, we found that the oocysts and eggs in tubes could be collected at a ratio of 2.00 to 3.08. Thus, our results indicate that the loop method is a simple and time saving method, implicating the application for the estimated OPG/ EPG (Oocysts/Eggs per gram) of the samples.
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Pollos , Heces , Animales , Heces/parasitología , Enfermedades de las Aves de Corral/parasitología , Enfermedades de las Aves de Corral/diagnóstico , Parasitosis Intestinales/veterinaria , Parasitosis Intestinales/diagnóstico , Parasitosis Intestinales/parasitología , Recuento de Huevos de Parásitos/veterinaria , Recuento de Huevos de Parásitos/métodos , Recuento de Huevos de Parásitos/instrumentación , Ascaridoidea/aislamiento & purificación , Oocistos/aislamiento & purificación , Eimeria/aislamiento & purificaciónRESUMEN
BACKGROUND: Opisthorchiid flukes, particularly Opisthorchis viverrini, Opisthorchis felineus, Clonorchis sinensis, and Metorchis spp. are the most common fish-borne zoonotic human liver flukes (hLFs). Liver fluke infections are more prevalent in resource-deprived and underprivileged areas. We herein estimated the prevalence of the metacercariae (MC) of major hLFs in common large freshwater fishes (lFWF) marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and reservoirs. METHODS: The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018-June 2022 using conventional and multiple molecular techniques, such as PCR, PCR-restriction fragment length polymorphism (RFLP), sequencing, and bioinformatic analyses. The infection rate of fishes was analyzed using the Z-test and the loads of MC were compared using the chi-squared (χ2) test. RESULTS: The MC of C. sinensis, Opisthorchis spp., and Metorchis spp. were detected in 11 species of common and popular lFWF. In lFWF, the estimated prevalence was 18.7% and the mean load was 137.4 ± 149.8 MC per 100 g of fish. The prevalence was the highest (P < 0.05) in spotted snakehead fishes (Channa punctata, 63.6%). The highest rate of infection (P < 0.05) was observed with the MC of C. sinensis (11.8%). Metacercariae were almost equally (P > 0.05) distributed between the head and body of fishes. The infection rate was slightly higher in cultured (19.6%) fishes. The MC of C. sinensis, O. felineus, O. viverrini, and Metorchis orientalis in fishes were confirmed using PCR, PCR-RFLP and bioinformatics. The cercariae of opisthorchiid (Pleurolophocercus cercariae) flukes were only recovered from Bithynia spp. (3.9%, 42 out of 1089). The ova of hLFs from dogs (4.3%, 5 out of 116) and cats (6.0%, 6 out of 100), and adult flukes (M. orientalis) from ducks (41.1% 113 out of 275) were detected. CONCLUSIONS: The MC of hLFs are highly prevalent in fresh water fishes in Bangladesh. Reservoir hosts, such as street dogs, cats, and ducks carried the patent infection, and residents of Bangladesh are at risk.
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Reservorios de Enfermedades , Enfermedades de los Peces , Peces , Agua Dulce , Zoonosis , Animales , Bangladesh/epidemiología , Peces/parasitología , Agua Dulce/parasitología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/epidemiología , Humanos , Reservorios de Enfermedades/parasitología , Reservorios de Enfermedades/veterinaria , Zoonosis/parasitología , Zoonosis/epidemiología , Zoonosis/transmisión , Vectores de Enfermedades , Prevalencia , Opisthorchis/genética , Opisthorchis/aislamiento & purificación , Metacercarias/genética , Metacercarias/aislamiento & purificación , Clonorchis sinensis/genética , Clonorchis sinensis/aislamiento & purificación , Moluscos/parasitologíaRESUMEN
The incorporation of saturated nitrogen-containing heterocycle 1,2,5-oxadiazinane into small molecules represents a compelling avenue in drug discovery due to its unexplored behavior within biological systems and incomplete protocols for synthesis. In this study, we present 1,2,5-oxadiazinane, an innovative heterocyclic bioisostere of piperizin-2-one and novel chemotype of the anti-schistosomal drug praziquantel (PZQ), which has been the only clinical drug available for three decades. PZQ is associated with significant drawbacks, including poor solubility, a bitter taste, and low metabolic stability. Therefore, the discovery of a new class of anti-schistosomal agents is imperative. To address this challenge, we introduce a pioneering method for the synthesis of 1,2,5-oxadiazinane derivatives through the cycloaddition of nitrones with N,N,N',N'-tetraalkyldiaminomethane in the presence of an IrIII complex photosensitizer. This transformative reaction offers a streamlined route to various kinds of 1,2,5-oxadiazinanes that is characterized by mild reaction conditions and broad substrate scope. Mechanistic investigations suggest that the photoredox pathway underlies the [3 + 3] photocycloaddition process. Thus, based on bioisosteric replacement, we identified a remarkable molecule as a new chemotype of a potent anti-schistosomal compound that not only exhibits superior solubility, but also retains the potent biological activity inherent to PZQ.
RESUMEN
[This corrects the article DOI: 10.1039/D4MD00599F.].
RESUMEN
Ixodid ticks are notorious blood-sucking ectoparasites and are completely dependent on blood-meals from hosts. In addition to the direct severe effects on health and productivity, ixodid ticks transmit various deadly diseases to humans and animals. Unlike rapidly feeding vessel-feeder hematophagous insects, the hard ticks feed on hosts for a long time (5-10 days or more), making a large blood pool beneath the skin. Tick's salivary glands produce a vast array of bio-molecules that modulate their complex and persistent feeding processes. However, the specific molecule that functions in the development and maintenance of a blood pool is yet to be identified. Recently, we have reported on longistatin, a 17.8-kDa protein with two functional EF-hand Ca(++)-binding domains, from the salivary glands of the disease vector, Haemaphysalis longicornis, that has been shown to be linked to blood-feeding processes. Here, we show that longistatin plays vital roles in the formation of a blood pool and in the acquisition of blood-meals. Data clearly revealed that post-transcriptional silencing of the longistatin-specific gene disrupted ticks' unique ability to create a blood pool, and they consequently failed to feed and replete on blood-meals from hosts. Longistatin completely hydrolyzed α, ß and γ chains of fibrinogen and delayed fibrin clot formation. Longistatin was able to bind with fibrin meshwork, and activated fibrin clot-bound plasminogen into its active form plasmin, as comparable to that of tissue-type plasminogen activator (t-PA), and induced lysis of fibrin clot and platelet-rich thrombi. Plasminogen activation potentiality of longistatin was increased up to 4 times by soluble fibrin. Taken together, our results suggest that longistatin may exert potent functions both as a plasminogen activator and as an anticoagulant in the complex scenario of blood pool formation; the latter is critical to the feeding success and survival of ixodid ticks.
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Sangre , Proteínas de Unión al Calcio/fisiología , Conducta Alimentaria/fisiología , Interacciones Huésped-Parásitos/fisiología , Ixodidae/fisiología , Activadores Plasminogénicos/fisiología , Proteínas Protozoarias/fisiología , Proteínas y Péptidos Salivales/fisiología , Animales , Anticoagulantes/metabolismo , Fibrina/metabolismo , Fibrinógeno/metabolismo , Fibrinolisina/metabolismo , ARN Bicatenario/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Around 25% of the global population suffer from one or more parasitic infections, of which food- and vector-borne parasitic zoonotic diseases are a major concern. Additionally, zoonoses and communicable diseases, common to man and animals, are drawing increased attention worldwide. Significant changes in climatic conditions, cropping pattern, demography, food habits, increasing international travel, marketing and trade, deforestation, and urbanization play vital roles in the emergence and re-emergence of parasitic zoonoses. Although it is likely to be underestimated, the collective burden of food- and vector-borne parasitic diseases accounts for â¼60 million disability-adjusted life years (DALYs). Out of 20 neglected tropical diseases (NTDs) listed by the World Health Organization (WHO) and the Centres for Disease Control and Prevention (CDC), 13 diseases are of parasitic origin. There are about 200 zoonotic diseases of which the WHO listed eight as neglected zoonotic diseases (NZDs) in the year 2013. Out of these eight NZDs, four diseases, namely cysticercosis, hydatidosis, leishmaniasis, and trypanosomiasis, are caused by parasites. In this review, we discuss the global burden and impacts of food- and vector-borne zoonotic parasitic diseases.
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Cisticercosis , Equinococosis , Parásitos , Enfermedades Parasitarias , Animales , Zoonosis/prevención & control , Enfermedades Parasitarias/epidemiología , Equinococosis/epidemiología , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/prevención & control , Salud GlobalRESUMEN
Human diphyllobothriasis, caused by Dibothriocephalus nihonkaiensis, is prevalent globally, especially in regions where raw fish is consumed. Recent molecular diagnostic techniques have made species identification of tapeworm parasites and the determination of genetic variations among parasite populations possible. However, only a few studies done over a decade ago, have reported on the genetic variation among D. nihonkaiensis in Japan. The present study employed PCR-based mitochondrial DNA analysis to specifically detect D. nihonkaiensis from archived clinical samples, and to determine any genetic variation that may exist among the Japanese broad tapeworms from patients of Kanagawa Prefecture, Japan. Target genes were amplified from DNA extracted from the ethanol- or formaldehyde-fixed samples by PCR. Further sequencing and comparative phylogenetic analyses based on mitochondrial COI and ND1 sequences were also performed. In our results, all PCR-amplified and sequenced samples were identified as D. nihonkaiensis. Analysis of COI sequences revealed two haplotype lineages. However, clustering of almost all COI (and ND1) sample sequences into one of the two haplotype clades, together with reference sequences from different countries worldwide, revealed a common haplotype among D. nihonkaiensis samples in our study. Our results suggest a possible presence of a dominant D. nihonkaiensis haplotype, with a global distribution circulating in Japan. Results from this study have the potential to improve the management of clinical cases and establish robust control measures to reduce the burden of human diphyllobothriasis in Japan.
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Cestodos , Infecciones por Cestodos , Difilobotriosis , Diphyllobothrium , Animales , Humanos , Haplotipos , Filogenia , Japón , Diphyllobothrium/genética , Cestodos/genética , Infecciones por Cestodos/veterinaria , Difilobotriosis/diagnóstico , Difilobotriosis/parasitología , Variación GenéticaRESUMEN
The mitochondria of adult and plerocercoid Spirometra mansoni were characterized in isolated mitochondria and in situ by electron microscopic histochemistry with special attention to the respiratory chain. Although the specific activities of the constituent enzyme complexes of succinate oxidase are fairly similar in adult and plerocercoid mitochondria, those of succinate oxidase and NADH-FRD are approximately 4- and 25-fold higher in adult mitochondria than in plerocercoid mitochondria, respectively. Quinone analysis by high performance liquid chromatography and mass spectrometry showed that adult and plerocercoid mitochondria contained both rhodoquinone-10 and ubiquinone-10 at concentrations of 4.98 and 0.106 nmol mg-1 for adult, and 0.677 and 0.137 nmol mg-1 for plerocercoid, respectively. Inhibition studies on the succinate-oxidase system of adult mitochondria showed that they possessed both cyanide-sensitive and -insensitive succinate oxidases, the latter of which produces hydrogen peroxide. Adult mitochondria, when NADH was used as a substrate, were shown to produce hydrogen peroxide, and the production of hydrogen peroxide decreased to undetectable levels in the presence of fumarate. The specific activities of NADH-fumarate reductase and cytochrome c oxidase were significantly higher in mature proglottids than in immature and gravid proglottids. Isopycnic density-gradient centrifugation analyses and in situ electron microscopic histochemistry revealed that both adult and plerocercoid mitochondria were heterogeneous in terms of respiratory function and physicochemical properties. The physiological significance of adult and plerocercoid mitochondria is discussed in relation to the oxygen tension of their parasitic habitats.
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Plerocercoide , Spirometra , Animales , Peróxido de Hidrógeno , Anaerobiosis , NAD , Mitocondrias , SuccinatosRESUMEN
RNA activation (RNAa) is a burgeoning area of research in which double-stranded RNAs (dsRNAs) or small activating RNAs mediate the upregulation of specific genes by targeting the promoter sequence and/or AU-rich elements in the 3'- untranslated region (3'-UTR) of mRNA molecules. So far, studies on the phenomenon have been limited to mammals, plants, bacteria, Caenorhabditis elegans, and recently, Aedes aegypti. However, it is yet to be applied in other arthropods, including ticks, despite the ubiquitous presence of argonaute 2 protein, which is an indispensable requirement for the formation of RNA-induced transcriptional activation complex to enable a dsRNA-mediated gene activation. In this study, we demonstrated for the first time the possible presence of RNAa phenomenon in the tick vector, Haemaphysalis longicornis (Asian longhorned tick). We targeted the 3'-UTR of a novel endochitinase-like gene (HlemCHT) identified previously in H. longicornis eggs for dsRNA-mediated gene activation. Our results showed an increased gene expression in eggs of H. longicornis endochitinase-dsRNA-injected (dsHlemCHT) ticks on day-13 post-oviposition. Furthermore, we observed that eggs of dsHlemCHT ticks exhibited relatively early egg development and hatching, suggesting a dsRNA-mediated activation of the HlemCHT gene in the eggs. This is the first attempt to provide evidence of RNAa in ticks. Although further studies are required to elucidate the detailed mechanism by which RNAa occurs in ticks, the outcome of this study provides new opportunities for the use of RNAa as a gene overexpression tool in future studies on tick biology, to reduce the global burden of ticks and tick-borne diseases.
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Ixodidae , Garrapatas , Animales , Femenino , Garrapatas/genética , Mosquitos Vectores , ARN Bicatenario/genética , Ixodidae/genética , ARN Mensajero , Mamíferos/genéticaRESUMEN
BACKGROUND: Mitochondrial (mt) genomes vary considerably in size, structure and gene content. The mt genomes of the phylum Apicomplexa, which includes important human pathogens such as the malaria parasite Plasmodium, also show marked diversity of structure. Plasmodium has a concatenated linear mt genome of the smallest size (6-kb); Babesia and Theileria have a linear monomeric mt genome (6.5-kb to 8.2-kb) with terminal inverted repeats; Eimeria, which is distantly related to Plasmodium and Babesia/Theileria, possesses a mt genome (6.2-kb) with a concatemeric form similar to that of Plasmodium; Cryptosporidium, the earliest branching lineage within the phylum Apicomplexa, has no mt genome. We are interested in the evolutionary origin of linear mt genomes of Babesia/Theileria, and have investigated mt genome structures in members of archaeopiroplasmid, a lineage branched off earlier from Babesia/Theileria. RESULTS: The complete mt genomes of archaeopiroplasmid parasites, Babesia microti and Babesia rodhaini, were sequenced. The mt genomes of B. microti (11.1-kb) and B. rodhaini (6.9-kb) possess two pairs of unique inverted repeats, IR-A and IR-B. Flip-flop inversions between two IR-As and between two IR-Bs appear to generate four distinct genome structures that are present at an equi-molar ratio. An individual parasite contained multiple mt genome structures, with 20 copies and 2 - 3 copies per haploid nuclear genome in B. microti and B. rodhaini, respectively. CONCLUSION: We found a novel linear monomeric mt genome structure of B. microti and B. rhodhaini equipped with dual flip-flop inversion system, by which four distinct genome structures are readily generated. To our knowledge, this study is the first to report the presence of two pairs of distinct IR sequences within a monomeric linear mt genome. The present finding provides insight into further understanding of evolution of mt genome structure.
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Babesia microti/genética , Evolución Molecular , Genoma Mitocondrial/genética , Conformación de Ácido Nucleico , Filogenia , Animales , Secuencia de Bases , Southern Blotting , Femenino , Secuencias Invertidas Repetidas/genética , Funciones de Verosimilitud , Ratones , Ratones Endogámicos ICR , Modelos Genéticos , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
Babesiosis is one of the most important tick-borne diseases affecting livestock that can cause major economic losses worldwide particularly in the tropics. Control relies on controlling both the protozoan parasite and the tick vector. Antiprotozoal drugs are most commonly used for treatment, but problems on emergence of resistant strains and food residues are encountered. Longicin, a defensin-like peptide identified from the hard tick, Haemapysalis longicornis, as well as one of its synthetic partial analogs (P4), were previously reported to exert antimicrobial, fungicidal, and parasiticidal activity. Both longicin and P4 showed babesiacidal activity, in vitro and in vivo. Here, peptide fragments of P4 were studied for in vitro activity against bovine Babesia parasites. One of the peptide fragments, antimicrobial peptide 1 (AMP1), reduced the parasitemia of Babesia bigemina. No peptide had significant effect on Babesia bovis. The sequence of AMP1 corresponded to the longicin sequence which is associated with antiparasitic activity. Although AMP1 caused reduction in parasitemia of B. bigemina, the difference in morphology of the parasite compared with the control group was not statistically significant. However, the percentage occurrence of piroplasms decreased, whereas the abnormal pycnotic form increased. The results demonstrated that this shorter peptide retained the anti-babesial activity of the parent peptide, exerting an antiparasitic effect against a bovine Babesia species. Therefore, this short peptide can be considered for chemical synthesis as an alternative therapeutic agent for babesiosis.
Asunto(s)
4-Butirolactona/análogos & derivados , Babesia/crecimiento & desarrollo , Babesiosis/veterinaria , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/parasitología , Fragmentos de Péptidos/farmacología , 4-Butirolactona/farmacología , Animales , Babesiosis/sangre , Babesiosis/tratamiento farmacológico , Babesiosis/parasitología , Bovinos , Enfermedades de los Bovinos/sangre , Eritrocitos/parasitología , Parasitemia/tratamiento farmacológicoRESUMEN
Echinostomes (Trematoda: Echinostomatidae) are food-borne zoonotic flatworms that affect birds, animals and humans, and has been classified as neglected tropical diseases (NTDs) by the World Health Organization (WHO), which cause severe enteritis in poultry and hamper production. Here, we confirmed the species of echinostomes affecting chickens in Bangladesh along with their genetic analyses, pathology and vectors. We isolated and identified adult worms from chickens, cercariae from fresh water snails and metacerariae (MC) from some wild fishes. We recovered Echinostoma revolutum (10.3%) and Hypoderaeum conoideum (6.0%) from chickens. Zoonotic E. revolutum was confirmed by amplifying nad1 gene and subsequent sequencing. Several mutations were detected in nad1 gene and our isolates belonged to the Euro-Asian clade. We observed thickening of mucosal layer, hyperplasia of goblet cells, infiltration of eosinophils, lymphocytes and must cells in the infected intestine. About 5.3% snails were infected and the highest percentage of infection was found in Lymnaea luteola (12.1%). Echinostome infection in snails was the highest in November (9.6%) and lowest in February (3.1%) in Bangladesh. MC of echinostomes were identified from blue panchax (Aplocheilus panchax) and tank goby (Glossogobius giuris). In conclusion, echinostomiasis is a notable big problem in indigenous chickens in Bangladesh and people, especially, villagers are at risk.
Asunto(s)
Echinostoma , Equinostomiasis , Animales , Bangladesh/epidemiología , Pollos , Echinostoma/genética , Equinostomiasis/veterinariaRESUMEN
Blood-feeding arthropods, particularly ticks and mosquitoes are considered the most important vectors of arthropod-borne diseases affecting humans and animals. While feeding on blood meals, arthropods are exposed to high levels of reactive oxygen species (ROS) since heme and other blood components can induce oxidative stress. Different ROS have important roles in interactions among the pathogens, vectors, and hosts. ROS influence various metabolic processes of the arthropods and some have detrimental effects. In this review, we investigate the various roles of ROS in these arthropods, including their innate immunity and the homeostasis of their microbiomes, that is, how ROS are utilized to maintain the balance between the natural microbiota and potential pathogens. We elucidate the mechanism of how ROS are utilized to fight off invading pathogens and how the arthropod-borne pathogens use the arthropods' antioxidant mechanism to defend against these ROS attacks and their possible impact on their vector potentials or their ability to acquire and transmit pathogens. In addition, we describe the possible roles of ROS in chemical insecticide/acaricide activity and/or in the development of resistance. Overall, this underscores the importance of the antioxidant system as a potential target for the control of arthropod and arthropod-borne pathogens.
RESUMEN
Schistosomiasis is a neglected tropical disease (NTD) caused by blood flukes (Schistosoma spp.). Schistosomatids affect a wide array of vertebrate hosts, including humans. In the present study, multiple species of schistosomatids were identified by isolating schistosomatid cercariae (SC) from naturally infected snails. We also described different biotic and abiotic factors influencing SC infections in snails and reported human cercarial dermatitis (HCD) for the first time in Bangladesh. A total of 22,012 snails of seven species: Lymnaea auricularia, L. luteola, Indoplanorbis exustus, Physa acuta, Viviparus bengalensis, Brotia spp., and Thiara spp., were collected and examined. Among these snails, 581 (2.6%) belonging to five species: L. luteola, L. auricularia, P. acuta, I. exustus, and V. bengalensis, were infected with SC. The rate of infection was the highest for L. luteola (11.1%), followed by L. auricularia (5.3%), and was the lowest for V. bengalensis (0.4%). Prevalence in snails was the highest in September (16.8%), followed by October (9.5%) and November (8.8%), and was the lowest in colder months, such as January (1.8%) and February (2.1%). Infections with schistosomatids were more common in larger snails and snails collected from sunny areas. We confirmed the presence of Schistosoma indicum, S. incognitum, S. nasale, S. spindale, and Trichobilharzia szidati by PCR and sequencing. Through a questionnaire survey, we detected HCD in 214 (53.5%) individuals, and the infection rate was almost equally distributed across all professions. Collectively, the present results suggest that lymnaeid snails are the main vector for Schistosoma spp. prevalent in Bangladesh, and schistosomatids with zoonotic potential are also prevalent.