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Comparative Medicine Oct 2023( ), the causative agent of the most commonly reported disease of zebrafish, is a microsporidian parasite that confounds research by inducing behavioral and...
( ), the causative agent of the most commonly reported disease of zebrafish, is a microsporidian parasite that confounds research by inducing behavioral and physiologic changes in zebrafish. Although a treatment for has not been documented in zebrafish, albendazole (ALB) and fumagillin (FUM) have been used to treat microsporidian infections of other fish species. To investigate the efficacy of oral ALB and FUM in the treatment of we performed a pilot study that demonstrated the safety and palatability of novel gel-based diets containing FUM or ALB in adult AB zebrafish. In a subsequent study, approximately 250 adult AB zebrafish (previously infected with ) were treated with these medicated diets for 4 wk. At 4 different time points (weeks 0, 5, 10, and 16 of the study), fish were euthanized and whole-body qPCR was performed to assess prevalence across treatment and control groups. There was no statistically significant association between treatment group and prevalence at any time point, although potential biologically relevant reductions in prevalence occurred in the combination therapy group at weeks 5 and 16 and in the ALB group at week 5. Based on high-performance liquid chromatography analyses, the medicated diets contained less ALB and more FUM than expected, highlighting the importance of validating medicated feed concentrations to ensure safety, efficacy, and consistency. While remains challenging to eradicate and control, results of this study warrant further investigation into the utility of ALB and FUM as potential treatments for this pathogen.
Topics: Animals; Zebrafish; Albendazole; Pilot Projects; Microsporidia
PubMed: 38087410
DOI: 10.30802/AALAS-CM-23-000035 -
International Journal of Molecular... Nov 2023(EHP) is a microsporidian parasite that infects , causing severe hepatopancreatic microsporidiosis (HPM) and resulting in significant economic losses. This study...
(EHP) is a microsporidian parasite that infects , causing severe hepatopancreatic microsporidiosis (HPM) and resulting in significant economic losses. This study utilizes a combined analysis of transcriptomics and metabolomics to unveil the dynamic molecular interactions between EHP and its host, the Pacific white shrimp, during the early and late stages of infection. The results indicate distinct immunological, detoxification, and antioxidant responses in the early and late infection phases. During early EHP infection in shrimp, immune activation coincides with suppression of genes like Ftz-F1 and SEPs, potentially aiding parasitic evasion. In contrast, late infection shows a refined immune response with phagocytosis-enhancing down-regulation of Ftz-F1 and a resurgence in SEP expression. This phase is characterized by an up-regulated detoxification and antioxidant response, likely a defense against the accumulated effects of EHP, facilitating a stable host-pathogen relationship. In the later stages of infection, most immune responses return to baseline levels, while some immune genes remain active. The glutathione antioxidant system is suppressed early on but becomes activated in the later stages. This phenomenon could facilitate the early invasion of EHP while assisting the host in mitigating oxidative damage caused by late-stage infection. Notably, there are distinctive events in polyamine metabolism. Sustained up-regulation of spermidine synthase and concurrent reduction in spermine levels suggest a potential role of polyamines in EHP development. Throughout the infection process, significant differences in genes such as ATP synthase and hexokinase highlight the continuous influence on energy metabolism pathways. Additionally, growth-related pathways involving amino acids such as tryptophan, histidine, and taurine are disrupted early on, potentially contributing to the growth inhibition observed during the initial stages of infection. In summary, these findings elucidate the dynamic interplay between the host, , and the parasite, EHP, during infection. Specific phase differences in immune responses, energy metabolism, and antioxidant processes underscore the intricate relationship between the host and the parasite. The disruption of polyamine metabolism offers a novel perspective in understanding the proliferation mechanisms of EHP. These discoveries significantly advance our comprehension of the pathogenic mechanisms of EHP and its interactions with the host.
Topics: Animals; Antioxidants; Enterocytozoon; Seafood; Penaeidae; Polyamines
PubMed: 38069062
DOI: 10.3390/ijms242316738 -
Animals : An Open Access Journal From... Nov 2023(EHP) is highly contagious and can cause hepatopancreatic microsporidiosis (HPM), which is typically characterized by the slow growth of shrimp. In this study, the...
(EHP) is highly contagious and can cause hepatopancreatic microsporidiosis (HPM), which is typically characterized by the slow growth of shrimp. In this study, the differences in histology, metabolism, oxidative stress and growth between healthy and EHP-infected were analyzed using an EHP challenge experiment. Histology showed that EHP caused lesions in the hepatic tubules of , such as hepatic tubular atrophy and epithelial cell shedding, with mature spores. Meanwhile, white feces may appear when the infection is severe. Furthermore, the content of total protein, glycogen, ATP and glucose in the EHP challenge group was significantly reduced. The qPCR results showed that EHP infection changed the expression of key genes in glucose metabolism, among which hexokinase (), phosphofructokinase (), pyruvatekinase (), citrate synthase () and isocitric dehydrogenase () were significantly down-regulated, while phosphoenolpyruvate carboxykinase (), fructose bisphosphatase () and glucose-6-phosphatase () were significantly up-regulated. Obviously, the expression of growth-related genes was disordered. Simultaneously, the antioxidant genes manganese superoxide dismutase (), catalase (), glutathione peroxidase (), glutathione-S-transferases () and nuclear factor E2-related factor2 () were up-regulated to varying degrees in the EHP challenge group, and EHP infection induced significant increases in the oxidative damage products lipid peroxide (LPO) and malondialdehyde (MDA). Ultimately, the shrimp weight of the challenge group was 6.85 ± 0.86 g, which was significantly lower than that of the control group (8.95 ± 0.75 g). Taken together, we speculate that EHP changes the substance metabolism and growth process by causing oxidative damage to the hepatopancreas, which may lead to the growth retardation of .
PubMed: 38067012
DOI: 10.3390/ani13233661 -
PLoS Neglected Tropical Diseases Dec 2023Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to...
Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. A bis-indole derivative, MMV1593539, decreased spore viability. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development.
Topics: Animals; Humans; Caenorhabditis elegans; Albendazole; Pandemics; Microsporidia; Microsporidiosis
PubMed: 38064503
DOI: 10.1371/journal.pntd.0011806 -
MBio Jan 2024is a symbiont with a strong malaria transmission-blocking phenotype in . It spreads in mosquito populations through mother-to-offspring and sexual transmission. The...
is a symbiont with a strong malaria transmission-blocking phenotype in . It spreads in mosquito populations through mother-to-offspring and sexual transmission. The ability of to block transmission, together with its ability to spread within populations and its avirulence to the host, makes it a very attractive candidate for developing a key strategy to stop malaria transmissions. Here, we report tissue tropism and localization patterns of , which are relevant to its transmission. We find that accumulates in tissues, linked to its sexual and vertical transmission. Its prevalence and intensity in the tissues over the mosquito life cycle suggest adaptation to maximize transmission and avirulence in . These findings provide the foundation for understanding the factors that may affect transmission efficiency. This will contribute to the development of strategies to maximize transmission to establish and sustain a high prevalence of the symbiont in mosquito populations for malaria transmission blocking.
Topics: Animals; Humans; Anopheles; Microsporidia; Malaria; Germ Cells; Tropism
PubMed: 38063396
DOI: 10.1128/mbio.02192-23 -
PLoS Pathogens Dec 2023Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming...
Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming industry. Nosema bombycis is a typical microsporidium that infects multiple lepidopteran insects via fecal-oral and transovarial transmission (TOT); however, the underlying TOT processes and mechanisms remain unknown. Here, we characterized the TOT process and identified key factors enabling N. bombycis to invade the ovariole and oocyte of silkworm Bombyx mori. We found that the parasites commenced with TOT at the early pupal stage when ovarioles penetrated the ovary wall and were exposed to the hemolymph. Subsequently, the parasites in hemolymph and hemolymph cells firstly infiltrated the ovariole sheath, from where they invaded the oocyte via two routes: (I) infecting follicular cells, thereby penetrating oocytes after proliferation, and (II) infecting nurse cells, thus entering oocytes following replication. In follicle and nurse cells, the parasites restructured and built large vacuoles to deliver themselves into the oocyte. In the whole process, the parasites were coated with B. mori vitellogenin (BmVg) on their surfaces. To investigate the BmVg effects on TOT, we suppressed its expression and found a dramatic decrease of pathogen load in both ovarioles and eggs, suggesting that BmVg plays a crucial role in the TOT. Thereby, we identified the BmVg domains and parasite spore wall proteins (SWPs) mediating the interaction, and demonstrated that the von Willebrand domain (VWD) interacted with SWP12, SWP26 and SWP30, and the unknown function domain (DUF1943) bound with the SWP30. When disrupting these interactions, we found significant reductions of the pathogen load in both ovarioles and eggs, suggesting that the interplays between BmVg and SWPs were vital for the TOT. In conclusion, our study has elucidated key aspects about the microsporidian TOT and revealed the key factors for understanding the molecular mechanisms underlying this transmission.
Topics: Animals; Humans; Vitellogenins; Spores, Fungal; Nosema; Bombyx
PubMed: 38060601
DOI: 10.1371/journal.ppat.1011859 -
Journal of Insect Science (Online) Nov 2023Honey bees are essential pollinators for several economically important crops. In temperate countries, honey bee colonies face multiple threats during the overwintering...
Honey bees are essential pollinators for several economically important crops. In temperate countries, honey bee colonies face multiple threats during the overwintering period, such as food availability, diseases, and confinement. Beekeepers commonly use chemicals to improve colony health during winter, but these products can have a negative impact on bee health and pathogens can develop resistance to them. Thus, there is a need for further development of alternative treatments. The aim of this study was to evaluate the impact of one endogenic bacterium (Bombella apis) and 2 commercial probiotic formulas (Bactocell and Levucell) on colony survival, spring development, and Vairimorpha (formerly Nosema) spp. spore count. Probiotic treatments were given in 1: 1 sugar syrup in October 2017 and April 2018, once a week for 2 wk. One experimental group was given Fumagilin-B, the only product approved in Canada to prevent nosemosis, once in October. The administration of 2 commercial probiotics, Bactocell (Pediococcus acidilactici) and Levucell (Saccharomyces cerevisiae boulardii), led to a significant increase in the number of sealed brood cells in spring. None of the probiotic treatments impacted the honey bee gut load of Vairimorpha spp. spores. The results suggest that beneficial microorganisms can improve spring development and performance of honey bee colonies.
Topics: Bees; Animals; Hymenoptera; Seasons; Probiotics; Nosema; Saccharomyces cerevisiae
PubMed: 38055938
DOI: 10.1093/jisesa/iead099 -
Parasite (Paris, France) 2023Metabarcoding is a powerful tool to detect classical, and well-known "long-branch" Microsporidia in environmental samples. Several primer pairs were developed to target...
Metabarcoding is a powerful tool to detect classical, and well-known "long-branch" Microsporidia in environmental samples. Several primer pairs were developed to target these unique microbial parasites, the majority of which remain undetected when using general metabarcoding primers. Most of these Microsporidia-targeting primer pairs amplify fragments of different length of the small subunit ribosomal RNA (SSU-rRNA) gene. However, we lack a broad comparison of the efficacy of those primers. Here, we conducted in silico PCRs with three short-read (which amplify a few-hundred base pairs) and two long-read (which amplify over a thousand base pairs) metabarcoding primer pairs on a variety of publicly available Microsporidia sensu lato SSU-rRNA gene sequences to test which primers capture most of the Microsporidia diversity. Our results indicate that the primer pairs do result in slight differences in inferred richness. Furthermore, some of the reverse primers are also able to bind to microsporidian subtaxa beyond the classical Microsporidia, which include the metchnikovellidan Amphiamblys spp., the chytridiopsid Chytridiopsis typographi and the "short-branch" microsporidian Mitosporidium daphniae.
Topics: Animals; DNA, Environmental; Microsporidia; Sequence Analysis, DNA; Phylogeny
PubMed: 38015008
DOI: 10.1051/parasite/2023056 -
Microbiology Spectrum Jan 2024The multiplex-crRNA CRISPR/Cas12a detection method saves hands-on time, reduces the risk of aerosol pollution, and can be directly applied to detecting silkworms...
The multiplex-crRNA CRISPR/Cas12a detection method saves hands-on time, reduces the risk of aerosol pollution, and can be directly applied to detecting silkworms infected with . This study provides a new approach for the inspection and quarantine of silkworm pébrine disease in sericulture and provides a new method for the detection of other pathogens.
Topics: Animals; CRISPR-Cas Systems; RNA, Guide, CRISPR-Cas Systems; Microsporidiosis; Nosema; Bombyx
PubMed: 38014967
DOI: 10.1128/spectrum.03014-23 -
Nature Communications Nov 2023Microsporidia are an early-diverging group of fungal pathogens with a wide host range. Several microsporidian species cause opportunistic infections in humans that can...
Microsporidia are an early-diverging group of fungal pathogens with a wide host range. Several microsporidian species cause opportunistic infections in humans that can be fatal. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on host metabolites for successful replication and development. Our knowledge of microsporidian intracellular development remains rudimentary, and our understanding of the intracellular niche occupied by microsporidia has relied on 2D TEM images and light microscopy. Here, we use serial block-face scanning electron microscopy (SBF-SEM) to capture 3D snapshots of the human-infecting species, Encephalitozoon intestinalis, within host cells. We track E. intestinalis development through its life cycle, which allows us to propose a model for how its infection organelle, the polar tube, is assembled de novo in developing spores. 3D reconstructions of parasite-infected cells provide insights into the physical interactions between host cell organelles and parasitophorous vacuoles, which contain the developing parasites. The host cell mitochondrial network is substantially remodeled during E. intestinalis infection, leading to mitochondrial fragmentation. SBF-SEM analysis shows changes in mitochondrial morphology in infected cells, and live-cell imaging provides insights into mitochondrial dynamics during infection. Our data provide insights into parasite development, polar tube assembly, and microsporidia-induced host mitochondria remodeling.
Topics: Animals; Humans; Microsporidia; Parasites; Imaging, Three-Dimensional; Encephalitozoon
PubMed: 37996434
DOI: 10.1038/s41467-023-43215-0