RARE DISEASE
Microsporidiosis
Microsporidiosis
Microsporidiosis
Drug discovery
1
drug
With orphan designation
Overview
Microsporidiosis is an emerging fungal parasitic infection caused by intracellular spore-forming Microsporidia, predominantly affecting immunocompromised individuals (e.g., advanced HIV/AIDS, transplant recipients). Common presentations include chronic diarrhea, keratoconjunctivitis, and systemic dissemination. Diagnosis relies on microscopic identification of spores in clinical samples or molecular methods. Treatment involves species-specific therapies such as albendazole for Encephalitozoon spp. and topical fumagillin for ocular disease, combined with immune restoration via antiretroviral therapy (ART) in HIV-associated cases [1][3][6][11].
Burden
Prevalence ranges from 2–50% in HIV-infected populations in low-resource regions; up to 6.6% global prevalence for E. bieneusi [4][7][16].
Associated with high morbidity (chronic wasting, malabsorption) and ~50% mortality in disseminated cases [2][5][12].
Limited treatment efficacy for E. bieneusi and diagnostic challenges amplify healthcare costs [3][7].
Therapies
First-line: Albendazole (400 mg BID) for Encephalitozoon spp.; ineffective against Enterocytozoon bieneusi. Topical fumagillin + albendazole for ocular disease [1][3][11].
HIV management: ART initiation/optimization critical for immune recovery, often resolving symptoms [6][11][17].
Adjunctive: Nutritional support, antimotility agents, and experimental therapies (e.g., nitazoxanide or fumagillin analogs) for refractory cases [3][7][16].
Categories: rare infectious diseases
Research Papers
410 drug discovery papers about Microsporidiosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
410 drug discovery papers about Microsporidiosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-08 | [A case of microsporidial keratoconjunctivitis].
A 15-year-old male patient presented with recurrent photophobia, lacrimation, and blurred vision in both eyes for 3 years. He had been repeatedly diagnosed with "bilateral keratitis (unknown etiology)"at other hospitals and failed to respond to multiple topical medications. Initially diagnosed as bilateral Thygeson superficial punctate keratitis, he was treated with 0.5% loteprednol etabonate suspension eye drops and other medications. However, his symptoms worsened after 3 weeks of treatment. Subsequently, corneal epithelial tissue metagenomic testing and scrape cytological examination were performed, confirming the diagnosis of bilateral microsporidial keratoconjunctivitis. The treatment regimen was adjusted to topical application of 1% voriconazole eye drops, 0.3% gatifloxacin ophthalmic gel, and 0.1% tacrolimus eye drops. After 3 weeks of treatment, the patient's visual acuity in both eyes recovered to 1.0, conjunctival hyperemia was alleviated, and corneal epithelial punctate infiltration and fluorescein staining improved. One month after treatment, his symptoms were basically relieved, with the corneal infiltration and palpebral conjunctival papillae resolved. No recurrence was observed during the one-year follow-up.
2026-05-18 | PI3K/Akt Signaling as a Potential Therapeutic Target for Reducing Inflammation and Corneal Stromal Injury in Microsporidial Stromal Keratitis.
This study aimed to investigate the role of the PI3K/Akt pathway in microsporidial stromal keratitis (MSK) and evaluate whether targeted inhibition of this pathway could provide a potential therapeutic strategy. A mouse model of MSK was established, followed by transcriptomic analysis to identify gene-expression changes following microsporidial infection. The activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was assessed through real-time quantitative polymerase chain reaction (RT-qPCR), immunostaining, and protein phosphorylation assays. To explore therapeutic implications, the PI3K/Akt inhibitor LY294002 was administered by subconjunctival injection, and its effects on corneal inflammation and cytokine production were assessed over the course of infection. Microsporidial infection markedly activated the PI3K/Akt pathway in the cornea, as evidenced by increased phosphorylation of PI3K and Akt. Transcriptomic analysis revealed upregulation of inflammatory cytokines, including MMP9, IL-1β, and TNF-α, indicating activation of inflammation-related pathways. Histologic analysis further confirmed increased immune cell infiltration and stromal edema in infected corneas. Pretreatment with LY294002 prior to infection alleviated the clinical manifestations of MSK, including corneal opacity, and reduced corneal expression of inflammatory expression levels, suggesting a contributory role of PI3K/Akt pathway in the pathogenesis and inflammation of MSK. PI3K/Akt signaling is a critical driver of inflammation in MSK. Targeting this pathway may present a promising strategy for the management of MSK. Future studies should focus on developing ocular-optimized inhibitors of the PI3K/Akt pathway and evaluating their safety and efficacy for potential clinical application in MSK treatment.
2026-03-18 | Detection of Enterocytozoon hepatopenaei in pond-cultured Litopenaeus vannamei shrimp: Unveiling the epidemiological significance of some invasive macrofauna, synergistic diagnostic approach and treatment trial.
Hepatopancreatic microsporidiosis (HPM) is protozoal disease caused by Enterocytozoon hepatopenaei (EHP), causing remarkable economic losses in the shrimp farming due to associated mortalities as well as size variations. The current study aimed to investigate the roles of some invasive macrofauna in the epidemiology of EHP, analyze the associated hepatopancreatic pathologies and check the efficacy of a novel field treatment for the EHP affected pond. A total of 100 L. vannamei were randomly collected from the affected pond before and after treatment trial. Samples were subjected to thorough clinical, parasitological and histopathological examination as well as molecular typing. A total of 5 moon jellyfish and 5 blue swimmer crabs were also collected from the affected ponds and subjected to parasitological examination. Significant size variations among sampled shrimp ranging from 2.1 g up to 20 g together with increased numbers of stunted shrimps were recorded. Behavioral changes such as poor feed response with/without white fecal threads were observed. The EHP spores in hepatopancreatic smears & impressions were identified using conventional methods by Giemsa and modified trichrome staining. The identity of the EHP spores was confirmed by the conventional PCR and sequencing of the PCR product. Histopathology revealed different degrees of degeneration at level of tubular epithelium and inter-tubular tissue together with random appearance of EHP spores. The moon jellyfish and blue swimmer crabs could play a role in EHP infection. The effectiveness of the used immunostimulatory & disinfection treatment protocol was confirmed by the remarkable reduction of the spore numbers in hepatopancreatic tissues.
2026-03-01 | The diagnostic challenge of Microsporidium keratoconjunctivitis: Case reports and literature review
Abstract The purpose of the study was to review the current medical evidence on Microsporidium keratoconjunctivitis (MKC) and to illustrate its clinical presentation, diagnostic challenges, and management through case reports. A comprehensive literature review was conducted using Google Scholar, PubMed, Scopus, and Embase to identify and synthesize available evidence on microsporidial keratoconjunctivitis, focusing on epidemiology, risk factors, clinical features, diagnostic methods, and treatment outcomes. In addition, two cases of MKC in immunocompetent young adults are presented to highlight common diagnostic challenges and clinical management. The literature consistently characterizes MKC as an uncommon but increasingly recognized cause of acute keratoconjunctivitis, frequently mistaken for viral or other nonspecific inflammatory entities. The disease typically presents with unilateral, multifocal, grayish-white corneal epithelial and subepithelial infiltrates, often associated with a follicular conjunctival response. Across published studies, delayed recognition and prior exposure to topical corticosteroids are recurrently linked to clinical deterioration. In our case series, initial misdiagnosis led to persistent or worsening symptoms despite corticosteroid or supportive therapy. Following initiation of topical 0.5% moxifloxacin monotherapy, both patients demonstrated prompt resolution of corneal lesions, complete visual recovery, and no evidence of recurrence. Microsporidiosis should be considered in the differential diagnosis of atypical keratoconjunctivitis that resembles viral infections, particularly when characteristic corneal lesions are present, and symptoms worsen with corticosteroids or do not improve with standard supportive therapy. Prompt recognition and appropriate management are crucial to prevent disease progression. Although fluoroquinolone monotherapy has been recommended and proved effective in these two cases, no established therapeutic regimen currently exists.
2025-11-08 | Evaluation of the use of vinpocetine in microsporidia infections.
Encephalitozoon intestinalis is a species of microsporidia that causes serious health problems, especially in immunocompromised individuals. The drug of choice for treatment today is albendazole. However, partial effects, resistance, and serious side effects are reported. Recently, vinpocetine has become a safe drug that is being investigated for the treatment of various diseases. In this study, the anti-microsporidial efficacies of vinpocetine, albendazole, and vinpocetine- albendazole combination, and how these combinations affected pathogen-induced tissue damage were assessed. In the study, male BALB/c mice were randomly divided into 6 groups. Except for the control groups, the other groups were infected with E. intestinalis spores after the application of cyclophosphamide. Treatments were started after the spores were detected by the Modified Trichrome method (MTS) in the stool samples. After five doses of treatment, spore load in stool samples was evaluated by MTS. Additionally, the sections obtained from the small intestines were stained with Masson's trichrome, and histopathological damage was evaluated. Although the spore load was higher in the group treated only with vinpocetine compared to the groups treated with albendazole, small intestinal damage was less. In addition, weight gain was observed in the group that was given vinpocetine and albendazole together. As a result, although the effect of vinpocetine on E. intestinalis virulence needs to be supported by larger studies, this study showed that vinpocetine alone has a positive effect on tissue damage. It has also been observed that it does not negatively alter the effectiveness of albendazole when used as a dietary supplement.
proteins
2026-05-07 | Lysozyme i1-type, a crucial antimicrobial enzyme, reduces Ecytonucleospora hepatopenaei infection in Litopenaeus vannamei with potential for feed supplementation.
Ecytonucleospora hepatopenaei (EHP) is a fungal-related microsporidian parasite that infects shrimp. EHP causes a hepatopancreatic microsporidiosis (HPM), resulting in growth retardation and increasing susceptibility to several secondary infections. Yet, the innate immune responses that effectively encounter EHP infection remain largely unknown. Here, we investigate the functions of Litopenaeus vannamei lysozyme-i1 (LvLyz-i1) in the shrimp's response to the EHP infection. LvLyz-i1 expression was strongly induced during EHP infection, showing ∼ 13-fold and ∼ 6000-fold upregulation in the hepatopancreas and hemocytes, respectively. Knockdown of LvLyz-i1 increased EHP loads and altered the expression of immune-related genes associated with the JAK/STAT, Toll, and IMD pathways. Recombinant LvLyz-i1 (rLvLyz-i1) exhibited antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, and Pichia pastoris, and displayed potential isopeptidase activity. Treatment of the EHP spores with rLvLyz-i1 caused damage to the polar tube, perhaps by digesting EHP polar tube proteins and reducing the transfer of infectious cargo to host cells. Dietary supplementation with rLvLyz-i1 significantly reduced EHP copies at 7 and 9 days post-cohabitation, while increasing the gene expression of other antimicrobial peptides and stress-related proteins. These results demonstrate that LvLyz-i1 plays a critical role in shrimp innate immunity and may serve as a promising strategy to protect against EHP infection.
2026-05-04 | Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn's Disease.
Crohn's disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case-control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in 50 CD patients and 50 matched healthy controls. Serum IL-7 and anti-E. cuniculi IgG, IgM, IgA and IgE were quantified by ELISA, while intestinal expression of IL-7, CD127 (IL-7Rα) and CD132 (IL-7Rγ) was assessed by RT-PCR. Protein levels of IL-7 and caspase-3 were evaluated by Western blot, and lymphocyte subsets and apoptosis by flow cytometry. CD patients showed reduced anti-E. cuniculi IgG and IgM levels but increased seropositivity, indicating compromised humoral quality despite greater exposure. Compared with controls, CD was associated with decreased serum IL-7, increased mucosal IL-7, downregulated CD132, and diminished caspase-3, suggesting a disrupted IL-7/IL-7R-apoptosis pathway. In CD, IgA- and IgE-skewed responses correlated differentially with caspase-3 and CD56+ γδ T cells, while E. cuniculi seropositivity independently predicted a shorter surgery-free interval. These findings identify a profound dysregulation of the IL-7/IL-7R-CD132-caspase-3 axis in CD and implicate E. cuniculi exposure as a potential marker of impaired mucosal immunity and adverse outcomes.
2025-02-24 | Characterization and functional analysis of the small heat shock protein HSP19.5 in Bombyx mori in response to Nosema bombycis infection.
Small heat shock proteins (sHSPs) are molecular chaperones known for their role in maintaining cellular homeostasis and protecting cells from various environmental stresses. This study focuses on the silkworm small heat shock protein HSP19.5 and its potential functions in the context of Nosema bombycis infection, a microsporidian pathogen causing severe disease in the sericulture industry. We cloned and characterized HSP19.5 and revealed its expression patterns in different silkworm tissues and developmental stages. Our results indicate that HSP19.5 expression is significantly up-regulated in response to N. bombycis infection, suggesting a role in the host stress response. Through a series of experiments, including RNA interference and overexpression analyses, we demonstrated that HSP19.5 promotes N. bombycis proliferation, possibly by inhibiting host cell apoptosis and regulating intracellular ROS levels. The cytoplasmic localization of HSP19.5 in silkworm cells is consistent with its function as a molecular chaperone. The results enhance our understanding of the complex host-pathogen interactions between silkworms and N. bombycis, and provides insights that may inform the development of novel strategies to control the pebrine disease.
2025-01-08 | Microsporidian Nosema bombycis secretes serine protease inhibitor to suppress host cell apoptosis via Caspase BmICE.
Microsporidia are a group of intracellular pathogens that actively manipulate host cell biological processes to facilitate their intracellular niche. Apoptosis is an important defense mechanism by which host cell control intracellular pathogens. Microsporidia modulating host cell apoptosis has been reported previously, however the molecular mechanism is not yet clear. In this report, we describe that the microsporidia Nosema bombycis inhibits apoptosis of Bombyx mori cells through a secreted protein NbSPN14, which is a serine protease inhibitor (Serpin). An immunofluorescent assay demonstrated that upon infection with N. bombycis, NbSPN14 was initially found in the B. mori cell cytoplasm and then became enriched in the host cell nucleus. Overexpression and RNA-interference (RNAi) of NbSPN14 in B. mori' embryo cell confirmed that NbSPN14 inhibited host cells apoptosis. Immunofluorescent and Co-IP assays verified the co-localization and interaction of NbSPN14 with the BmICE, the Caspase 3 homolog in B. mori. Knocking out of BmICE or mutating the BmICE-interacting P1 site of NbSPN14, eliminated the localization of NbSPN14 into the host nucleus and prevented the apoptosis-inhibiting effect of NbSPN14, which also proved that the interaction between BmICE and NbSPN14 occurred in host cytoplasm and the NbSPN14 translocation into host cell nucleus depends on BmICE. These data elucidate that N. bombycis secretory protein NbSPN14 inhibits host cell apoptosis by directly inhibiting the Caspase protease BmICE, which provides an important insight for understanding pathogen-host interactions and a potential therapeutic target for N. bombycis proliferation.
2024-05-09 | Immune signaling of Litopenaeus vannamei c-type lysozyme and its role during microsporidian Enterocytozoon hepatopenaei (EHP) infection.
The microsporidian Enterocytozoon hepatopenaei (EHP) is a fungi-related, spore-forming parasite. EHP infection causes growth retardation and size variation in shrimp, resulting in severe economic losses. Studies on shrimp immune response have shown that several antimicrobial peptides (AMPs) were upregulated upon EHP infection. Among those highly upregulated AMPs is c-type lysozyme (LvLyz-c). However, the immune signaling pathway responsible for LvLyz-c production in shrimp as well as its function against the EHP infection are still poorly understood. Here, we characterized major shrimp immune signaling pathways and found that Toll and JAK/STAT pathways were up-regulated upon EHP infection. Knocking down of a Domeless (DOME) receptor in the JAK/STAT pathways resulted in a significant reduction of the LvLyz-c and the elevation of EHP copy number. We further elucidated the function of LvLyz-c by heterologously expressing a recombinant LvLyz-c (rLvLyz-c) in an Escherichia coli. rLvLyz-c exhibited antibacterial activity against several bacteria such as Bacillus subtilis and Vibrio parahaemolyticus. Interestingly, we found an antifungal activity of rLvLyz-c against Candida albican, which led us to further investigate the effects of rLvLyz-c on EHP spores. Incubation of the EHP spores with rLvLyz-c followed by a chitin staining showed that the signals were dramatically decreased in a dose-dependent manner, suggesting that rLvLyz-c possibly digest a chitin coat on the EHP spores. Transmission electron microscopy analysis revealed that an endospore layer, which is composed mainly of chitin, was digested by rLvLyz-c. Lastly, we observed that EHP spores that were treated with rLvLyz-c showed a significant reduction of the spore germination rate. We hypothesize that thinning of the endospore of EHP would result in altered permeability, hence affecting spore germination. This work provides insights into shrimp immune signaling pathways responsible for LvLyz-c production and its anti-EHP property. This knowledge will serve as important foundations for developing EHP control strategies.
cell therapies
2026-01-11 | Rainbow trout gut epithelial cells upregulate MHCII transcript expression in response to experimental infection with the anglerfish parasite Spraguea americanus.
The microsporidia are a group of obligate intracellular parasites implicated in the collapse of numerous North American fisheries and aquaculture industries over the past century. Although the majority of fish-infecting microsporidia are transmitted via ingestion, very little is known regarding the role of gut epithelial cells in anti-microsporidian immunity. In the absence of cell lines from Lophiid fishes, the present study investigates this phenomenon via experimental infection of the rainbow trout gut epithelial cell line RTgutGC with spores of the anglerfish parasite Spraguea americanus. As early as 1-day post-infection, mature spores attached to the plasma membranes of RTgut cells and induced spore uptake via an endocytic process. After uptake, spores persisted within individual, tight-fitting endosomes for 2 weeks, during which no lysosome/phagolysosome fusion or spore degradation was observed. Moreover, infected RTgut cells upregulated transcripts encoding the MHCII (Major histocompatibility class 2) alpha and beta chains while downregulating transcripts encoding the invariant chain (14-1), the 35 kDa subunit of IL-12, IL-1β and the class I component β2 m (beta-2 microglobulin). While S. americanus spores were ultimately incapable of germinating and developing within RTgut cells, these observations indicate that the cell line RTgutGC may possess M-cell-like characteristics and that gut epithelial cells may play a crucial role in sampling and presenting exogenous antigens during the initial stages of microsporidia infection in teleosts. To this end, future use of this novel in vitro infection can inform the development of novel strategies to protect susceptible finfish stocks from microsporidia outbreaks, thus helping these industries keep pace with growing global demands for fish protein.
2022-05-16 | Immune Response to Microsporidia.
Microsporidia are a group of pathogens, which can pose severe risks to the immunocompromised population, such as HIV-infected individuals or organ transplant recipients. Adaptive immunity has been reported to be critical for protection, and mice depleted of T cells are unable to control these infections. In a mouse model of infection, CD8 T cells have been found to be the primary effector cells and are responsible for protecting the infected host. Also, as infection is acquired via a peroral route, CD8 T cells in the gut compartment act as a first line of defense against these pathogens. Thus, generation of a robust CD8 T-cell response exhibiting polyfunctional ability is critical for host survival. In this chapter, we describe the effector CD8 T cells generated during microsporidia infection and the factors that may be essential for generating protective immunity against these understudied but significant pathogens. Overall, this chapter will highlight the necessity for a better understanding of the development of CD8 T-cell responses in gut-associated lymphoid tissue (GALT) and provide some insights into therapies that may be used to restore defective CD8 T-cell functionality in an immunocompromised situation.
2022-02-02 | Mice with genetic and induced B-cell deficiency as a model for disseminated encephalitozoonosis.
Encephalitozoon cuniculi, an intracellular pathogen, lives in a balanced relationship with immunocompetent individuals based on the activity of T lymphocytes. We previously highlighted the greater susceptibility of B-1 cell-deficient mice (XID mice) to encephalitozoonosis. This study aimed to develop a model of disseminated and severe encephalitozoonosis in mice with combined immunodeficiency to elucidate the role of B cells. To address this objective, cyclophosphamide (Cy)-treated BALB/c and XID mice were inoculated with E. cuniculi, followed by the evaluation of the immune response and histopathological lesions. Immunosuppressed BALB/c mice manifested no clinical signs with an increase in the populations of T lymphocytes and macrophages in the spleen. Immunosuppressed and infected XID mice revealed elevated T cells, macrophages populations, and pro-inflammatory cytokines levels (IFN-γ, TNF-α, and IL-6) with the presence of abdominal effusion and lesions in multiple organs. These clinical characteristics are associated with extensive and severe encephalitozoonosis. The symptoms and lesion size were reduced, whereas B-2 and CD4+ T cells populations were increased in the spleen by transferring B-2 cells adoptive to XID mice. Moreover, B-1 cells adoptive transfer upregulated the peritoneal populations of B-2 cells and macrophages but not T lymphocytes and decreased the symptoms. Herein, we speculated the consistency in the development of severe and disseminated encephalitozoonosis in mice with genetic deficiency of Bruton's tyrosine kinase (Btk) associated with Cy immunosuppression develop with that of the models with T cell deficiency. Taken together, these data emphasized the crucial role of B cells in the protective immune response against encephalitozoonosis.
2020-01-10 | B-1 cell-mediated modulation of M1 macrophage profile ameliorates microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi.
Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.
2018-11-26 | B-1 cells upregulate CD8 T lymphocytes and increase proinflammatory cytokines serum levels in oral encephalitozoonosis.
Microsporidia are intracellular pathogens that cause severe disease in immunocompromised humans and animals. We recently demonstrated that XID mice are more susceptible to Encephalitozoon cuniculi infection by intraperitoneal route, evidencing the role of B-1 cells in resistance against infection. The present study investigated the resistance and susceptibility against E. cuniculi oral infection, including the role of B-1 cells. BALB/c and BALB/c XID (B-1 cells deficient) mice were orally infected with E. cuniculi spores. No clinical symptoms were observed in infected animals; histopathology showed lymphoplasmocytic enteritis with degeneration of the apexes of the villi in all infected groups. Higher parasite burden was observed in infected BALB/c XID mice. In the spleen and peritoneum, all infected mice showed a decrease of lymphocytes, including CD8+ T cells, mostly in infected BALB/c XID mice. Adoptive transfer of B-1 cells (XID + B-1) was associated with a lower parasite burden. Pro-inflammatory cytokines (IFN-γ, TNF-α and IL-6) increased mostly in infected XID + B1 mice. Together, the present results showed that BALB/c XID mice infected by the oral route were more susceptible to encephalitozoonosis than BALB/c mice, demonstrating the B-1 cells importance in the control of the immune response against oral E. cuniculi infection.
antibodies
2023-12-16 | A monoclonal antibody targeting spore wall protein 1 inhibits the proliferation of Nosema bombycis in Bombyx mori.
There are a few reports on the resistance of microsporidia, including Nosema bombycis. Here, the alkali-soluble germination proteins of N. bombycis were used as immunogens to prepare a monoclonal antibody, and its single-chain variable fragments effectively blocked microsporidia infection. Our study has provided novel strategies for microsporidiosis control and demonstrated a useful method for the potential treatment of other microsporidia diseases.
2022-12-04 | Construction of scFv Antibodies against the Outer Loops of the Microsporidium Nosema bombycis ATP/ADP-Transporters and Selection of the Fragment Efficiently Inhibiting Parasite Growth
Traditional sanitation practices remain the main strategy for controlling Bombyx mori infections caused by microsporidia Nosema bombycis. This actualizes the development of new approaches to increase the silkworm resistance to this parasite. Here, we constructed a mouse scFv library against the outer loops of N. bombycis ATP/ADP carriers and selected nine scFv fragments to the transporter, highly expressed in the early stages of the parasite intracellular growth. Expression of selected scFv genes in Sf9 cells, their infection with different ratios of microsporidia spores per insect cell, qPCR analysis of N. bombycis PTP2 and Spodoptera frugiperda COXI transcripts in 100 infected cultures made it possible to select the scFv fragment most effectively inhibiting the parasite growth. Western blot analysis of 42 infected cultures with Abs against the parasite β-tubulin confirmed its inhibitory efficiency. Since the VL part of this scFv fragment was identified as a human IgG domain retained from the pSEX81 phagemid during library construction, its VH sequence should be a key antigen-recognizing determinant. Along with the further selection of new recombinant Abs, this suggests the searching for its natural mouse VL domain or “camelization” of the VH fragment by introducing cysteine and hydrophilic residues, as well as the randomization of its CDRs.
2021-10-20 | Microsporidia infection in patients with autoimmune diseases.
Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for <2 months of duration (P < 0.05). There was a significant increase in microsporidia infection in autoimmune disease patients undergoing treatment with TNF-α antagonists, and the duration of treatment is one of the risk factors. The study highlights the importance of microsporidia testing in immunocompromised patients, particularly those undergoing treatment with anti-TNF-α drugs and emphasises the need for awareness among clinicians regarding this opportunistic parasite.
2017-09-26 | The role of microsporidian polar tube protein 4 (PTP4) in host cell infection.
Microsporidia have been identified as pathogens that have important effects on our health, food security and economy. A key to the success of these obligate intracellular pathogens is their unique invasion organelle, the polar tube, which delivers the nucleus containing sporoplasm into host cells during invasion. Due to the size of the polar tube, the rapidity of polar tube discharge and sporoplasm passage, and the absence of genetic techniques for the manipulation of microsporidia, study of this organelle has been difficult and there is relatively little known regarding polar tube formation and the function of the proteins making up this structure. Herein, we have characterized polar tube protein 4 (PTP4) from the microsporidium Encephalitozoon hellem and found that a monoclonal antibody to PTP4 labels the tip of the polar tube suggesting that PTP4 might be involved in a direct interaction with host cell proteins during invasion. Further analyses employing indirect immunofluorescence (IFA), enzyme-linked immunosorbent (ELISA) and fluorescence-activated cell sorting (FACS) assays confirmed that PTP4 binds to mammalian cells. The addition of either recombinant PTP4 protein or anti-PTP4 antibody reduced microsporidian infection of its host cells in vitro. Proteomic analysis of PTP4 bound to host cell membranes purified by immunoprecipitation identified transferrin receptor 1 (TfR1) as a potential host cell interacting partner for PTP4. Additional experiments revealed that knocking out TfR1, adding TfR1 recombinant protein into cell culture, or adding anti-TfR1 antibody into cell culture significantly reduced microsporidian infection rates. These results indicate that PTP4 is an important protein competent of the polar tube involved in the mechanism of host cell infection utilized by these pathogens.
2016-02-02 | Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism
Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNg, CD4+ and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1b or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNg secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNg secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development towards cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation.
other
2023-12-22 | Enterocytozoon hepatopenaei Infection in Shrimp: Diagnosis, Interventions, and Food Safety Guidelines
The emergence of disease in shrimp has governed much concern in food safety and security among consumers with the recent reports on hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP). The microsporidians present in shrimp remain a silent pathogen that prevents optimal shrimp growth. However, the biggest threat is in its food safety concerns, which is the primary focus in ensuring food biosecurity and biosafety. Hence, the objective of this review is to summarise the current knowledge of EHP and its infection in shrimp with food safety concerns. This paper provides an analysis of the diagnostic methods for detecting EHP infections in shrimp aquaculture. Interventions with current molecular biology and biotechnology would be the second approach to addressing EHP diseases. Finally, a systematic guideline for shrimp food safety using diagnostic and intervention is proposed. Thus, this review was aimed to shed light on effective methods for the diagnosis and prevention of EHP infection in shrimp. We also include information on molecular and genomics tools as well as innate immune biomolecules as future targets in the intervention strategies on the microsporidsosis life cycle in shrimp and its environment. Overall, this will result in reduced disease outbreaks in shrimp aquaculture, ensuring the shrimp food safety in the future.
2023-01-20 | Identification and subcellular localization analysis of membrane protein Ycf 1 in the microsporidian Nosema bombycis.
Microsporidia are obligate intracellular parasites that can infect a wide range of vertebrates and invertebrates including humans and insects, such as silkworm and bees. The microsporidium Nosema bombycis can cause pebrine in Bombyx mori, which is the most destructive disease in the sericulture industry. Although membrane proteins are involved in a wide range of cellular functions and part of many important metabolic pathways, there are rare reports about the membrane proteins of microsporidia up to now. We screened a putative membrane protein Ycf 1 from the midgut transcriptome of the N. bombycis-infected silkworm. Gene cloning and bioinformatics analysis showed that the Ycf 1 gene contains a complete open reading frame (ORF) of 969 bp in length encoding a 322 amino acid polypeptide that has one signal peptide and one transmembrane domain. Indirect immunofluorescence results showed that Ycf 1 protein is distributed on the plasma membrane. Expression pattern analysis showed that the Ycf 1 gene expressed in all developmental stages of N. bombycis. Knockdown of the Ycf 1 gene by RNAi effectively inhibited the proliferation of N. bombycis. These results indicated that Ycf 1 is a membrane protein and plays an important role in the life cycle of N. bombycis.
2021-06-22 | Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera.
Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.
2021-04-29 | Construction and heterologous overexpression of two chimeric proteins carrying outer hydrophilic loops of Vairimorpha ceranae and Nosema bombycis ATP/ADP carriers.
Microsporidia Nosema bombycis and Vairimorpha ceranae cause destructive epizootics of honey bees and silkworms. Insufficient efficiency of the antibiotic fumagillin against V. ceranae, its toxicity and the absence of effective methods of N. bombycis treatment demand the discovery of novel strategies to suppress infections of domesticated insects. RNA interference is one such novel treatment strategy. Another one implies that the intracellular development of microsporidia may be suppressed by single-chain antibodies (scFv fragments) against functionally important parasite proteins. Important components of microsporidian metabolism are non-mitochondrial, plastidic-bacterial ATP/ADP carriers. These membrane transporters import host-derived ATP and provide the capacity to pathogens for energy parasitism. Here, we analyzed membrane topology of four V. ceranae and three N. bombycis ATP/ADP transporters to construct two fusion proteins carrying their outer hydrophilic loops contacting with infected host cell cytoplasm. Interestingly, full-size genes of N. bombycis transporters may be derived from the Asian swallowtail Papilio xuthus genome sequencing project. Synthesis of the artificial genes was followed by overexpression of recombinant proteins in E. coli as insoluble inclusion bodies. The gene fragments encoding the loops of individual transporters were also effectively expressed in bacteria. The chimeric antigens may be used to construct immune libraries or select microsporidia-suppressing scFv fragments from synthetic, semisynthetic, naïve and immune antibody libraries. A further expression of such antibodies in insect cells may increase their resistance to microsporidial infections.
2021-01-12 | Increased survival of the honey bee Apis mellifera infected with the microsporidian Nosema ceranae by effective gene silencing.
This study examined the control of nosemosis caused by Nosema ceranae, one of the hard-to-control diseases of honey bees, using RNA interference (RNAi) technology. Double-stranded RNA (dsRNA) for RNAi application targeted the mitosome-related genes of N. ceranae. Among the various mitosome-related genes, NCER_100882, NCER_101456, NCER_100157, and NCER_100686 exhibited relatively low homologies with the orthologs of Apis mellifera. Four gene-specific dsRNAs were prepared against the target genes and applied to the infected A. mellifera to analyze Nosema proliferation and honey bee survival. Two dsRNAs specifics to NCER_101456 and NCER_100157 showed high inhibitory effects on spore production by exhibiting only 62% and 67%, respectively, compared with the control. In addition, these dsRNA treatments significantly rescued the honey bees from the fatal nosemosis. It was confirmed that the inhibition of Nosema spore proliferation and the increase in the survival rate of honey bees were resulted from a decrease in the expression level of each target gene by dsRNA treatment. However, dsRNA mixture treatment was no more effective than single treatments in the rescue from the nosemosis. It is expected that the four newly identified mitosome-related target genes in this study can be effectively used for nosemosis control using RNAi technology.
small molecules
2026-06-08 | [A case of microsporidial keratoconjunctivitis].
A 15-year-old male patient presented with recurrent photophobia, lacrimation, and blurred vision in both eyes for 3 years. He had been repeatedly diagnosed with "bilateral keratitis (unknown etiology)"at other hospitals and failed to respond to multiple topical medications. Initially diagnosed as bilateral Thygeson superficial punctate keratitis, he was treated with 0.5% loteprednol etabonate suspension eye drops and other medications. However, his symptoms worsened after 3 weeks of treatment. Subsequently, corneal epithelial tissue metagenomic testing and scrape cytological examination were performed, confirming the diagnosis of bilateral microsporidial keratoconjunctivitis. The treatment regimen was adjusted to topical application of 1% voriconazole eye drops, 0.3% gatifloxacin ophthalmic gel, and 0.1% tacrolimus eye drops. After 3 weeks of treatment, the patient's visual acuity in both eyes recovered to 1.0, conjunctival hyperemia was alleviated, and corneal epithelial punctate infiltration and fluorescein staining improved. One month after treatment, his symptoms were basically relieved, with the corneal infiltration and palpebral conjunctival papillae resolved. No recurrence was observed during the one-year follow-up.
2026-05-18 | PI3K/Akt Signaling as a Potential Therapeutic Target for Reducing Inflammation and Corneal Stromal Injury in Microsporidial Stromal Keratitis.
This study aimed to investigate the role of the PI3K/Akt pathway in microsporidial stromal keratitis (MSK) and evaluate whether targeted inhibition of this pathway could provide a potential therapeutic strategy. A mouse model of MSK was established, followed by transcriptomic analysis to identify gene-expression changes following microsporidial infection. The activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was assessed through real-time quantitative polymerase chain reaction (RT-qPCR), immunostaining, and protein phosphorylation assays. To explore therapeutic implications, the PI3K/Akt inhibitor LY294002 was administered by subconjunctival injection, and its effects on corneal inflammation and cytokine production were assessed over the course of infection. Microsporidial infection markedly activated the PI3K/Akt pathway in the cornea, as evidenced by increased phosphorylation of PI3K and Akt. Transcriptomic analysis revealed upregulation of inflammatory cytokines, including MMP9, IL-1β, and TNF-α, indicating activation of inflammation-related pathways. Histologic analysis further confirmed increased immune cell infiltration and stromal edema in infected corneas. Pretreatment with LY294002 prior to infection alleviated the clinical manifestations of MSK, including corneal opacity, and reduced corneal expression of inflammatory expression levels, suggesting a contributory role of PI3K/Akt pathway in the pathogenesis and inflammation of MSK. PI3K/Akt signaling is a critical driver of inflammation in MSK. Targeting this pathway may present a promising strategy for the management of MSK. Future studies should focus on developing ocular-optimized inhibitors of the PI3K/Akt pathway and evaluating their safety and efficacy for potential clinical application in MSK treatment.
2026-03-18 | Detection of Enterocytozoon hepatopenaei in pond-cultured Litopenaeus vannamei shrimp: Unveiling the epidemiological significance of some invasive macrofauna, synergistic diagnostic approach and treatment trial.
Hepatopancreatic microsporidiosis (HPM) is protozoal disease caused by Enterocytozoon hepatopenaei (EHP), causing remarkable economic losses in the shrimp farming due to associated mortalities as well as size variations. The current study aimed to investigate the roles of some invasive macrofauna in the epidemiology of EHP, analyze the associated hepatopancreatic pathologies and check the efficacy of a novel field treatment for the EHP affected pond. A total of 100 L. vannamei were randomly collected from the affected pond before and after treatment trial. Samples were subjected to thorough clinical, parasitological and histopathological examination as well as molecular typing. A total of 5 moon jellyfish and 5 blue swimmer crabs were also collected from the affected ponds and subjected to parasitological examination. Significant size variations among sampled shrimp ranging from 2.1 g up to 20 g together with increased numbers of stunted shrimps were recorded. Behavioral changes such as poor feed response with/without white fecal threads were observed. The EHP spores in hepatopancreatic smears & impressions were identified using conventional methods by Giemsa and modified trichrome staining. The identity of the EHP spores was confirmed by the conventional PCR and sequencing of the PCR product. Histopathology revealed different degrees of degeneration at level of tubular epithelium and inter-tubular tissue together with random appearance of EHP spores. The moon jellyfish and blue swimmer crabs could play a role in EHP infection. The effectiveness of the used immunostimulatory & disinfection treatment protocol was confirmed by the remarkable reduction of the spore numbers in hepatopancreatic tissues.
2026-03-01 | The diagnostic challenge of Microsporidium keratoconjunctivitis: Case reports and literature review
Abstract The purpose of the study was to review the current medical evidence on Microsporidium keratoconjunctivitis (MKC) and to illustrate its clinical presentation, diagnostic challenges, and management through case reports. A comprehensive literature review was conducted using Google Scholar, PubMed, Scopus, and Embase to identify and synthesize available evidence on microsporidial keratoconjunctivitis, focusing on epidemiology, risk factors, clinical features, diagnostic methods, and treatment outcomes. In addition, two cases of MKC in immunocompetent young adults are presented to highlight common diagnostic challenges and clinical management. The literature consistently characterizes MKC as an uncommon but increasingly recognized cause of acute keratoconjunctivitis, frequently mistaken for viral or other nonspecific inflammatory entities. The disease typically presents with unilateral, multifocal, grayish-white corneal epithelial and subepithelial infiltrates, often associated with a follicular conjunctival response. Across published studies, delayed recognition and prior exposure to topical corticosteroids are recurrently linked to clinical deterioration. In our case series, initial misdiagnosis led to persistent or worsening symptoms despite corticosteroid or supportive therapy. Following initiation of topical 0.5% moxifloxacin monotherapy, both patients demonstrated prompt resolution of corneal lesions, complete visual recovery, and no evidence of recurrence. Microsporidiosis should be considered in the differential diagnosis of atypical keratoconjunctivitis that resembles viral infections, particularly when characteristic corneal lesions are present, and symptoms worsen with corticosteroids or do not improve with standard supportive therapy. Prompt recognition and appropriate management are crucial to prevent disease progression. Although fluoroquinolone monotherapy has been recommended and proved effective in these two cases, no established therapeutic regimen currently exists.
2025-11-08 | Evaluation of the use of vinpocetine in microsporidia infections.
Encephalitozoon intestinalis is a species of microsporidia that causes serious health problems, especially in immunocompromised individuals. The drug of choice for treatment today is albendazole. However, partial effects, resistance, and serious side effects are reported. Recently, vinpocetine has become a safe drug that is being investigated for the treatment of various diseases. In this study, the anti-microsporidial efficacies of vinpocetine, albendazole, and vinpocetine- albendazole combination, and how these combinations affected pathogen-induced tissue damage were assessed. In the study, male BALB/c mice were randomly divided into 6 groups. Except for the control groups, the other groups were infected with E. intestinalis spores after the application of cyclophosphamide. Treatments were started after the spores were detected by the Modified Trichrome method (MTS) in the stool samples. After five doses of treatment, spore load in stool samples was evaluated by MTS. Additionally, the sections obtained from the small intestines were stained with Masson's trichrome, and histopathological damage was evaluated. Although the spore load was higher in the group treated only with vinpocetine compared to the groups treated with albendazole, small intestinal damage was less. In addition, weight gain was observed in the group that was given vinpocetine and albendazole together. As a result, although the effect of vinpocetine on E. intestinalis virulence needs to be supported by larger studies, this study showed that vinpocetine alone has a positive effect on tissue damage. It has also been observed that it does not negatively alter the effectiveness of albendazole when used as a dietary supplement.
proteins
2026-05-07 | Lysozyme i1-type, a crucial antimicrobial enzyme, reduces Ecytonucleospora hepatopenaei infection in Litopenaeus vannamei with potential for feed supplementation.
Ecytonucleospora hepatopenaei (EHP) is a fungal-related microsporidian parasite that infects shrimp. EHP causes a hepatopancreatic microsporidiosis (HPM), resulting in growth retardation and increasing susceptibility to several secondary infections. Yet, the innate immune responses that effectively encounter EHP infection remain largely unknown. Here, we investigate the functions of Litopenaeus vannamei lysozyme-i1 (LvLyz-i1) in the shrimp's response to the EHP infection. LvLyz-i1 expression was strongly induced during EHP infection, showing ∼ 13-fold and ∼ 6000-fold upregulation in the hepatopancreas and hemocytes, respectively. Knockdown of LvLyz-i1 increased EHP loads and altered the expression of immune-related genes associated with the JAK/STAT, Toll, and IMD pathways. Recombinant LvLyz-i1 (rLvLyz-i1) exhibited antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, and Pichia pastoris, and displayed potential isopeptidase activity. Treatment of the EHP spores with rLvLyz-i1 caused damage to the polar tube, perhaps by digesting EHP polar tube proteins and reducing the transfer of infectious cargo to host cells. Dietary supplementation with rLvLyz-i1 significantly reduced EHP copies at 7 and 9 days post-cohabitation, while increasing the gene expression of other antimicrobial peptides and stress-related proteins. These results demonstrate that LvLyz-i1 plays a critical role in shrimp innate immunity and may serve as a promising strategy to protect against EHP infection.
2026-05-04 | Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn's Disease.
Crohn's disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case-control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in 50 CD patients and 50 matched healthy controls. Serum IL-7 and anti-E. cuniculi IgG, IgM, IgA and IgE were quantified by ELISA, while intestinal expression of IL-7, CD127 (IL-7Rα) and CD132 (IL-7Rγ) was assessed by RT-PCR. Protein levels of IL-7 and caspase-3 were evaluated by Western blot, and lymphocyte subsets and apoptosis by flow cytometry. CD patients showed reduced anti-E. cuniculi IgG and IgM levels but increased seropositivity, indicating compromised humoral quality despite greater exposure. Compared with controls, CD was associated with decreased serum IL-7, increased mucosal IL-7, downregulated CD132, and diminished caspase-3, suggesting a disrupted IL-7/IL-7R-apoptosis pathway. In CD, IgA- and IgE-skewed responses correlated differentially with caspase-3 and CD56+ γδ T cells, while E. cuniculi seropositivity independently predicted a shorter surgery-free interval. These findings identify a profound dysregulation of the IL-7/IL-7R-CD132-caspase-3 axis in CD and implicate E. cuniculi exposure as a potential marker of impaired mucosal immunity and adverse outcomes.
2025-02-24 | Characterization and functional analysis of the small heat shock protein HSP19.5 in Bombyx mori in response to Nosema bombycis infection.
Small heat shock proteins (sHSPs) are molecular chaperones known for their role in maintaining cellular homeostasis and protecting cells from various environmental stresses. This study focuses on the silkworm small heat shock protein HSP19.5 and its potential functions in the context of Nosema bombycis infection, a microsporidian pathogen causing severe disease in the sericulture industry. We cloned and characterized HSP19.5 and revealed its expression patterns in different silkworm tissues and developmental stages. Our results indicate that HSP19.5 expression is significantly up-regulated in response to N. bombycis infection, suggesting a role in the host stress response. Through a series of experiments, including RNA interference and overexpression analyses, we demonstrated that HSP19.5 promotes N. bombycis proliferation, possibly by inhibiting host cell apoptosis and regulating intracellular ROS levels. The cytoplasmic localization of HSP19.5 in silkworm cells is consistent with its function as a molecular chaperone. The results enhance our understanding of the complex host-pathogen interactions between silkworms and N. bombycis, and provides insights that may inform the development of novel strategies to control the pebrine disease.
2025-01-08 | Microsporidian Nosema bombycis secretes serine protease inhibitor to suppress host cell apoptosis via Caspase BmICE.
Microsporidia are a group of intracellular pathogens that actively manipulate host cell biological processes to facilitate their intracellular niche. Apoptosis is an important defense mechanism by which host cell control intracellular pathogens. Microsporidia modulating host cell apoptosis has been reported previously, however the molecular mechanism is not yet clear. In this report, we describe that the microsporidia Nosema bombycis inhibits apoptosis of Bombyx mori cells through a secreted protein NbSPN14, which is a serine protease inhibitor (Serpin). An immunofluorescent assay demonstrated that upon infection with N. bombycis, NbSPN14 was initially found in the B. mori cell cytoplasm and then became enriched in the host cell nucleus. Overexpression and RNA-interference (RNAi) of NbSPN14 in B. mori' embryo cell confirmed that NbSPN14 inhibited host cells apoptosis. Immunofluorescent and Co-IP assays verified the co-localization and interaction of NbSPN14 with the BmICE, the Caspase 3 homolog in B. mori. Knocking out of BmICE or mutating the BmICE-interacting P1 site of NbSPN14, eliminated the localization of NbSPN14 into the host nucleus and prevented the apoptosis-inhibiting effect of NbSPN14, which also proved that the interaction between BmICE and NbSPN14 occurred in host cytoplasm and the NbSPN14 translocation into host cell nucleus depends on BmICE. These data elucidate that N. bombycis secretory protein NbSPN14 inhibits host cell apoptosis by directly inhibiting the Caspase protease BmICE, which provides an important insight for understanding pathogen-host interactions and a potential therapeutic target for N. bombycis proliferation.
2024-05-09 | Immune signaling of Litopenaeus vannamei c-type lysozyme and its role during microsporidian Enterocytozoon hepatopenaei (EHP) infection.
The microsporidian Enterocytozoon hepatopenaei (EHP) is a fungi-related, spore-forming parasite. EHP infection causes growth retardation and size variation in shrimp, resulting in severe economic losses. Studies on shrimp immune response have shown that several antimicrobial peptides (AMPs) were upregulated upon EHP infection. Among those highly upregulated AMPs is c-type lysozyme (LvLyz-c). However, the immune signaling pathway responsible for LvLyz-c production in shrimp as well as its function against the EHP infection are still poorly understood. Here, we characterized major shrimp immune signaling pathways and found that Toll and JAK/STAT pathways were up-regulated upon EHP infection. Knocking down of a Domeless (DOME) receptor in the JAK/STAT pathways resulted in a significant reduction of the LvLyz-c and the elevation of EHP copy number. We further elucidated the function of LvLyz-c by heterologously expressing a recombinant LvLyz-c (rLvLyz-c) in an Escherichia coli. rLvLyz-c exhibited antibacterial activity against several bacteria such as Bacillus subtilis and Vibrio parahaemolyticus. Interestingly, we found an antifungal activity of rLvLyz-c against Candida albican, which led us to further investigate the effects of rLvLyz-c on EHP spores. Incubation of the EHP spores with rLvLyz-c followed by a chitin staining showed that the signals were dramatically decreased in a dose-dependent manner, suggesting that rLvLyz-c possibly digest a chitin coat on the EHP spores. Transmission electron microscopy analysis revealed that an endospore layer, which is composed mainly of chitin, was digested by rLvLyz-c. Lastly, we observed that EHP spores that were treated with rLvLyz-c showed a significant reduction of the spore germination rate. We hypothesize that thinning of the endospore of EHP would result in altered permeability, hence affecting spore germination. This work provides insights into shrimp immune signaling pathways responsible for LvLyz-c production and its anti-EHP property. This knowledge will serve as important foundations for developing EHP control strategies.
cell therapies
2026-01-11 | Rainbow trout gut epithelial cells upregulate MHCII transcript expression in response to experimental infection with the anglerfish parasite Spraguea americanus.
The microsporidia are a group of obligate intracellular parasites implicated in the collapse of numerous North American fisheries and aquaculture industries over the past century. Although the majority of fish-infecting microsporidia are transmitted via ingestion, very little is known regarding the role of gut epithelial cells in anti-microsporidian immunity. In the absence of cell lines from Lophiid fishes, the present study investigates this phenomenon via experimental infection of the rainbow trout gut epithelial cell line RTgutGC with spores of the anglerfish parasite Spraguea americanus. As early as 1-day post-infection, mature spores attached to the plasma membranes of RTgut cells and induced spore uptake via an endocytic process. After uptake, spores persisted within individual, tight-fitting endosomes for 2 weeks, during which no lysosome/phagolysosome fusion or spore degradation was observed. Moreover, infected RTgut cells upregulated transcripts encoding the MHCII (Major histocompatibility class 2) alpha and beta chains while downregulating transcripts encoding the invariant chain (14-1), the 35 kDa subunit of IL-12, IL-1β and the class I component β2 m (beta-2 microglobulin). While S. americanus spores were ultimately incapable of germinating and developing within RTgut cells, these observations indicate that the cell line RTgutGC may possess M-cell-like characteristics and that gut epithelial cells may play a crucial role in sampling and presenting exogenous antigens during the initial stages of microsporidia infection in teleosts. To this end, future use of this novel in vitro infection can inform the development of novel strategies to protect susceptible finfish stocks from microsporidia outbreaks, thus helping these industries keep pace with growing global demands for fish protein.
2022-05-16 | Immune Response to Microsporidia.
Microsporidia are a group of pathogens, which can pose severe risks to the immunocompromised population, such as HIV-infected individuals or organ transplant recipients. Adaptive immunity has been reported to be critical for protection, and mice depleted of T cells are unable to control these infections. In a mouse model of infection, CD8 T cells have been found to be the primary effector cells and are responsible for protecting the infected host. Also, as infection is acquired via a peroral route, CD8 T cells in the gut compartment act as a first line of defense against these pathogens. Thus, generation of a robust CD8 T-cell response exhibiting polyfunctional ability is critical for host survival. In this chapter, we describe the effector CD8 T cells generated during microsporidia infection and the factors that may be essential for generating protective immunity against these understudied but significant pathogens. Overall, this chapter will highlight the necessity for a better understanding of the development of CD8 T-cell responses in gut-associated lymphoid tissue (GALT) and provide some insights into therapies that may be used to restore defective CD8 T-cell functionality in an immunocompromised situation.
2022-02-02 | Mice with genetic and induced B-cell deficiency as a model for disseminated encephalitozoonosis.
Encephalitozoon cuniculi, an intracellular pathogen, lives in a balanced relationship with immunocompetent individuals based on the activity of T lymphocytes. We previously highlighted the greater susceptibility of B-1 cell-deficient mice (XID mice) to encephalitozoonosis. This study aimed to develop a model of disseminated and severe encephalitozoonosis in mice with combined immunodeficiency to elucidate the role of B cells. To address this objective, cyclophosphamide (Cy)-treated BALB/c and XID mice were inoculated with E. cuniculi, followed by the evaluation of the immune response and histopathological lesions. Immunosuppressed BALB/c mice manifested no clinical signs with an increase in the populations of T lymphocytes and macrophages in the spleen. Immunosuppressed and infected XID mice revealed elevated T cells, macrophages populations, and pro-inflammatory cytokines levels (IFN-γ, TNF-α, and IL-6) with the presence of abdominal effusion and lesions in multiple organs. These clinical characteristics are associated with extensive and severe encephalitozoonosis. The symptoms and lesion size were reduced, whereas B-2 and CD4+ T cells populations were increased in the spleen by transferring B-2 cells adoptive to XID mice. Moreover, B-1 cells adoptive transfer upregulated the peritoneal populations of B-2 cells and macrophages but not T lymphocytes and decreased the symptoms. Herein, we speculated the consistency in the development of severe and disseminated encephalitozoonosis in mice with genetic deficiency of Bruton's tyrosine kinase (Btk) associated with Cy immunosuppression develop with that of the models with T cell deficiency. Taken together, these data emphasized the crucial role of B cells in the protective immune response against encephalitozoonosis.
2020-01-10 | B-1 cell-mediated modulation of M1 macrophage profile ameliorates microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi.
Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response.
2018-11-26 | B-1 cells upregulate CD8 T lymphocytes and increase proinflammatory cytokines serum levels in oral encephalitozoonosis.
Microsporidia are intracellular pathogens that cause severe disease in immunocompromised humans and animals. We recently demonstrated that XID mice are more susceptible to Encephalitozoon cuniculi infection by intraperitoneal route, evidencing the role of B-1 cells in resistance against infection. The present study investigated the resistance and susceptibility against E. cuniculi oral infection, including the role of B-1 cells. BALB/c and BALB/c XID (B-1 cells deficient) mice were orally infected with E. cuniculi spores. No clinical symptoms were observed in infected animals; histopathology showed lymphoplasmocytic enteritis with degeneration of the apexes of the villi in all infected groups. Higher parasite burden was observed in infected BALB/c XID mice. In the spleen and peritoneum, all infected mice showed a decrease of lymphocytes, including CD8+ T cells, mostly in infected BALB/c XID mice. Adoptive transfer of B-1 cells (XID + B-1) was associated with a lower parasite burden. Pro-inflammatory cytokines (IFN-γ, TNF-α and IL-6) increased mostly in infected XID + B1 mice. Together, the present results showed that BALB/c XID mice infected by the oral route were more susceptible to encephalitozoonosis than BALB/c mice, demonstrating the B-1 cells importance in the control of the immune response against oral E. cuniculi infection.
antibodies
2023-12-16 | A monoclonal antibody targeting spore wall protein 1 inhibits the proliferation of Nosema bombycis in Bombyx mori.
There are a few reports on the resistance of microsporidia, including Nosema bombycis. Here, the alkali-soluble germination proteins of N. bombycis were used as immunogens to prepare a monoclonal antibody, and its single-chain variable fragments effectively blocked microsporidia infection. Our study has provided novel strategies for microsporidiosis control and demonstrated a useful method for the potential treatment of other microsporidia diseases.
2022-12-04 | Construction of scFv Antibodies against the Outer Loops of the Microsporidium Nosema bombycis ATP/ADP-Transporters and Selection of the Fragment Efficiently Inhibiting Parasite Growth
Traditional sanitation practices remain the main strategy for controlling Bombyx mori infections caused by microsporidia Nosema bombycis. This actualizes the development of new approaches to increase the silkworm resistance to this parasite. Here, we constructed a mouse scFv library against the outer loops of N. bombycis ATP/ADP carriers and selected nine scFv fragments to the transporter, highly expressed in the early stages of the parasite intracellular growth. Expression of selected scFv genes in Sf9 cells, their infection with different ratios of microsporidia spores per insect cell, qPCR analysis of N. bombycis PTP2 and Spodoptera frugiperda COXI transcripts in 100 infected cultures made it possible to select the scFv fragment most effectively inhibiting the parasite growth. Western blot analysis of 42 infected cultures with Abs against the parasite β-tubulin confirmed its inhibitory efficiency. Since the VL part of this scFv fragment was identified as a human IgG domain retained from the pSEX81 phagemid during library construction, its VH sequence should be a key antigen-recognizing determinant. Along with the further selection of new recombinant Abs, this suggests the searching for its natural mouse VL domain or “camelization” of the VH fragment by introducing cysteine and hydrophilic residues, as well as the randomization of its CDRs.
2021-10-20 | Microsporidia infection in patients with autoimmune diseases.
Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for <2 months of duration (P < 0.05). There was a significant increase in microsporidia infection in autoimmune disease patients undergoing treatment with TNF-α antagonists, and the duration of treatment is one of the risk factors. The study highlights the importance of microsporidia testing in immunocompromised patients, particularly those undergoing treatment with anti-TNF-α drugs and emphasises the need for awareness among clinicians regarding this opportunistic parasite.
2017-09-26 | The role of microsporidian polar tube protein 4 (PTP4) in host cell infection.
Microsporidia have been identified as pathogens that have important effects on our health, food security and economy. A key to the success of these obligate intracellular pathogens is their unique invasion organelle, the polar tube, which delivers the nucleus containing sporoplasm into host cells during invasion. Due to the size of the polar tube, the rapidity of polar tube discharge and sporoplasm passage, and the absence of genetic techniques for the manipulation of microsporidia, study of this organelle has been difficult and there is relatively little known regarding polar tube formation and the function of the proteins making up this structure. Herein, we have characterized polar tube protein 4 (PTP4) from the microsporidium Encephalitozoon hellem and found that a monoclonal antibody to PTP4 labels the tip of the polar tube suggesting that PTP4 might be involved in a direct interaction with host cell proteins during invasion. Further analyses employing indirect immunofluorescence (IFA), enzyme-linked immunosorbent (ELISA) and fluorescence-activated cell sorting (FACS) assays confirmed that PTP4 binds to mammalian cells. The addition of either recombinant PTP4 protein or anti-PTP4 antibody reduced microsporidian infection of its host cells in vitro. Proteomic analysis of PTP4 bound to host cell membranes purified by immunoprecipitation identified transferrin receptor 1 (TfR1) as a potential host cell interacting partner for PTP4. Additional experiments revealed that knocking out TfR1, adding TfR1 recombinant protein into cell culture, or adding anti-TfR1 antibody into cell culture significantly reduced microsporidian infection rates. These results indicate that PTP4 is an important protein competent of the polar tube involved in the mechanism of host cell infection utilized by these pathogens.
2016-02-02 | Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism
Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNg, CD4+ and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1b or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNg secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNg secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development towards cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation.
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2023-12-22 | Enterocytozoon hepatopenaei Infection in Shrimp: Diagnosis, Interventions, and Food Safety Guidelines
The emergence of disease in shrimp has governed much concern in food safety and security among consumers with the recent reports on hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP). The microsporidians present in shrimp remain a silent pathogen that prevents optimal shrimp growth. However, the biggest threat is in its food safety concerns, which is the primary focus in ensuring food biosecurity and biosafety. Hence, the objective of this review is to summarise the current knowledge of EHP and its infection in shrimp with food safety concerns. This paper provides an analysis of the diagnostic methods for detecting EHP infections in shrimp aquaculture. Interventions with current molecular biology and biotechnology would be the second approach to addressing EHP diseases. Finally, a systematic guideline for shrimp food safety using diagnostic and intervention is proposed. Thus, this review was aimed to shed light on effective methods for the diagnosis and prevention of EHP infection in shrimp. We also include information on molecular and genomics tools as well as innate immune biomolecules as future targets in the intervention strategies on the microsporidsosis life cycle in shrimp and its environment. Overall, this will result in reduced disease outbreaks in shrimp aquaculture, ensuring the shrimp food safety in the future.
2023-01-20 | Identification and subcellular localization analysis of membrane protein Ycf 1 in the microsporidian Nosema bombycis.
Microsporidia are obligate intracellular parasites that can infect a wide range of vertebrates and invertebrates including humans and insects, such as silkworm and bees. The microsporidium Nosema bombycis can cause pebrine in Bombyx mori, which is the most destructive disease in the sericulture industry. Although membrane proteins are involved in a wide range of cellular functions and part of many important metabolic pathways, there are rare reports about the membrane proteins of microsporidia up to now. We screened a putative membrane protein Ycf 1 from the midgut transcriptome of the N. bombycis-infected silkworm. Gene cloning and bioinformatics analysis showed that the Ycf 1 gene contains a complete open reading frame (ORF) of 969 bp in length encoding a 322 amino acid polypeptide that has one signal peptide and one transmembrane domain. Indirect immunofluorescence results showed that Ycf 1 protein is distributed on the plasma membrane. Expression pattern analysis showed that the Ycf 1 gene expressed in all developmental stages of N. bombycis. Knockdown of the Ycf 1 gene by RNAi effectively inhibited the proliferation of N. bombycis. These results indicated that Ycf 1 is a membrane protein and plays an important role in the life cycle of N. bombycis.
2021-06-22 | Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera.
Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.
2021-04-29 | Construction and heterologous overexpression of two chimeric proteins carrying outer hydrophilic loops of Vairimorpha ceranae and Nosema bombycis ATP/ADP carriers.
Microsporidia Nosema bombycis and Vairimorpha ceranae cause destructive epizootics of honey bees and silkworms. Insufficient efficiency of the antibiotic fumagillin against V. ceranae, its toxicity and the absence of effective methods of N. bombycis treatment demand the discovery of novel strategies to suppress infections of domesticated insects. RNA interference is one such novel treatment strategy. Another one implies that the intracellular development of microsporidia may be suppressed by single-chain antibodies (scFv fragments) against functionally important parasite proteins. Important components of microsporidian metabolism are non-mitochondrial, plastidic-bacterial ATP/ADP carriers. These membrane transporters import host-derived ATP and provide the capacity to pathogens for energy parasitism. Here, we analyzed membrane topology of four V. ceranae and three N. bombycis ATP/ADP transporters to construct two fusion proteins carrying their outer hydrophilic loops contacting with infected host cell cytoplasm. Interestingly, full-size genes of N. bombycis transporters may be derived from the Asian swallowtail Papilio xuthus genome sequencing project. Synthesis of the artificial genes was followed by overexpression of recombinant proteins in E. coli as insoluble inclusion bodies. The gene fragments encoding the loops of individual transporters were also effectively expressed in bacteria. The chimeric antigens may be used to construct immune libraries or select microsporidia-suppressing scFv fragments from synthetic, semisynthetic, naïve and immune antibody libraries. A further expression of such antibodies in insect cells may increase their resistance to microsporidial infections.
2021-01-12 | Increased survival of the honey bee Apis mellifera infected with the microsporidian Nosema ceranae by effective gene silencing.
This study examined the control of nosemosis caused by Nosema ceranae, one of the hard-to-control diseases of honey bees, using RNA interference (RNAi) technology. Double-stranded RNA (dsRNA) for RNAi application targeted the mitosome-related genes of N. ceranae. Among the various mitosome-related genes, NCER_100882, NCER_101456, NCER_100157, and NCER_100686 exhibited relatively low homologies with the orthologs of Apis mellifera. Four gene-specific dsRNAs were prepared against the target genes and applied to the infected A. mellifera to analyze Nosema proliferation and honey bee survival. Two dsRNAs specifics to NCER_101456 and NCER_100157 showed high inhibitory effects on spore production by exhibiting only 62% and 67%, respectively, compared with the control. In addition, these dsRNA treatments significantly rescued the honey bees from the fatal nosemosis. It was confirmed that the inhibition of Nosema spore proliferation and the increase in the survival rate of honey bees were resulted from a decrease in the expression level of each target gene by dsRNA treatment. However, dsRNA mixture treatment was no more effective than single treatments in the rescue from the nosemosis. It is expected that the four newly identified mitosome-related target genes in this study can be effectively used for nosemosis control using RNAi technology.
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Drug Discovery Landscape
1 orphan drug designation for Microsporidiosis.
1 orphan drug designation for Microsporidiosis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Bacillus thuringiensis crystal protein (Cry5B) | — | FDA | 2018-03-07 | — | University of Massachusetts Medical School |
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