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Clinical Microbiology Reviews Dec 2021Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are...
Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are about 220 genera and 1,700 species of microsporidia, which are classified based on their ultrastructural features, developmental cycle, host-parasite relationship, and molecular analysis. Phylogenetic analysis suggests that microsporidia are related to the fungi, being grouped with the Cryptomycota as a basal branch or sister group to the fungi. Microsporidia can be transmitted by food and water and are likely zoonotic, as they parasitize a wide range of invertebrate and vertebrate hosts. Infection in humans occurs in both immunocompetent and immunodeficient hosts, e.g., in patients with organ transplantation, patients with advanced human immunodeficiency virus (HIV) infection, and patients receiving immune modulatory therapy such as anti-tumor necrosis factor alpha antibody. Clusters of infections due to latent infection in transplanted organs have also been demonstrated. Gastrointestinal infection is the most common manifestation; however, microsporidia can infect virtually any organ system, and infection has resulted in keratitis, myositis, cholecystitis, sinusitis, and encephalitis. Both albendazole and fumagillin have efficacy for the treatment of various species of microsporidia; however, albendazole has limited efficacy for the treatment of Enterocytozoon bieneusi. In addition, immune restoration can lead to resolution of infection. While the prevalence rate of microsporidiosis in patients with AIDS has fallen in the United States, due to the widespread use of combination antiretroviral therapy (cART), infection continues to occur throughout the world and is still seen in the United States in the setting of cART if a low CD4 count persists.
Topics: Gastrointestinal Diseases; Humans; Microsporidia; Microsporidiosis; Phylogeny; Prevalence
PubMed: 34190570
DOI: 10.1128/CMR.00010-20 -
Current Opinion in Microbiology Aug 2015Microsporidia comprise one of the largest groups of obligate intracellular pathogens and can infect virtually all animals, but host response to these fungal-related... (Review)
Review
Microsporidia comprise one of the largest groups of obligate intracellular pathogens and can infect virtually all animals, but host response to these fungal-related microbes has been poorly understood. Several new studies of the host transcriptional response to microsporidia infection have found infection-induced regulation of genes involved in innate immunity, ubiquitylation, metabolism, and hormonal signaling. In addition, microsporidia have recently been shown to exploit host recycling endocytosis for exit from intestinal cells, and to interact with host degradation pathways. Microsporidia infection has also been shown to profoundly affect behavior in insect hosts. Altogether, these and other recent findings are providing much-needed insight into the underlying mechanisms of microsporidia interaction with host animals.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Immunity, Innate; Insecta; Microsporidia; Microsporidiosis
PubMed: 25847674
DOI: 10.1016/j.mib.2015.03.006 -
Trends in Parasitology Oct 2017Microsporidia may cause emerging infectious diseases (EIDs) in bumblebees. Two drivers - commercial bumblebees and managed honey bees - have been identified as possible... (Review)
Review
Microsporidia may cause emerging infectious diseases (EIDs) in bumblebees. Two drivers - commercial bumblebees and managed honey bees - have been identified as possible sources of pathogen spillover. In addition, declines in bumblebee populations may have led to lower genetic diversity and subsequent higher susceptibility to infection, enabling microsporidia to increase in prevalence. There is strong evidence for relatively recent increases in the prevalence of Nosema bombi in North America. However, the lack of definitive data on spillover by microsporidia, in North America or elsewhere, makes it difficult to identify the causes of such increases. Phylogenomic studies are urgently needed to identify the global population structure of microsporidia in bumblebees, and thus identify the source of current and future epidemics.
Topics: Animals; Bees; Genetic Variation; North America; Nosema; Phylogeny
PubMed: 28663099
DOI: 10.1016/j.pt.2017.06.001 -
Journal of Clinical Microbiology Nov 2014Microsporidia are highly specialized obligate intracellular organisms that are closely related to fungi. Although traditionally associated with diarrheal illness in... (Review)
Review
Microsporidia are highly specialized obligate intracellular organisms that are closely related to fungi. Although traditionally associated with diarrheal illness in patients with AIDS, extraintestinal infections involving various organs have been reported with increasing frequency in the past decade, particularly in immunocompromised hosts. Diagnosis is usually accomplished by light microscopic identification of spores in body fluids and tissues, using a variety of stains. Transmission electron microscopy, immunofluorescence assays, or molecular methods are necessary for identification to the genus and species level. Early diagnosis is essential for preventing the significant associated morbidity and mortality of extraintestinal microsporidiosis.
Topics: Humans; Immunocompromised Host; Microbiological Techniques; Microsporidia; Microsporidiosis
PubMed: 24829239
DOI: 10.1128/JCM.00971-14 -
Expert Opinion on Therapeutic Targets Nov 2018Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidiosis is chronic diarrhea, a significant mortality risk in... (Review)
Review
Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidiosis is chronic diarrhea, a significant mortality risk in immune-compromised patients. Albendazole, which inhibits tubulin, and fumagillin, which inhibits methionine aminopeptidase type 2 (MetAP2), are the two main therapeutic agents used for treatment of microsporidiosis. In addition, to their role as emerging pathogens in humans, microsporidia are important pathogens in insects, aquaculture, and veterinary medicine. New therapeutic targets and therapies have become a recent focus of attention for medicine, veterinary, and agricultural use. Areas covered: Herein, we discuss the detection and symptoms of microsporidiosis in humans and the therapeutic targets that have been utilized for the design of new drugs for the treatment of this infection, including triosephosphate isomerase, tubulin, MetAP2, topoisomerase IV, chitin synthases, and polyamines. Expert opinion: Enterocytozoon bieneusi is the most common microsporidia in human infection. Fumagillin has a broader anti-microsporidian activity than albendazole and is active against both Ent. bieneusi and Encephaliozoonidae. Microsporidia lack methionine aminopeptidase type 1 and are, therefore, dependent on MetAP2, while mammalian cells have both enzymes. Thus, MetAP2 is an essential enzyme in microsporidia and new inhibitors of this pathway have significant promise as therapeutic agents.
Topics: Albendazole; Animals; Antifungal Agents; Cyclohexanes; Drug Design; Fatty Acids, Unsaturated; Humans; Microsporidia; Microsporidiosis; Molecular Targeted Therapy; Sesquiterpenes
PubMed: 30336698
DOI: 10.1080/14728222.2018.1538360 -
Revista Chilena de Infectologia :... 2018
Topics: Microsporidia; Microsporidiosis
PubMed: 29652974
DOI: 10.4067/s0716-10182018000100073 -
Developmental and Comparative Immunology Nov 2016Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This... (Review)
Review
Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This review is focused on microscopic parasites (Protozoa and Metazoa) that invade the gastrointestinal tract of fish. Intracellular parasites (mainly Microsporidia and Apicomplexa) evoke almost no host immune reaction while they are concealed in the cytoplasmic and nuclear compartments, and can even use fish cells (macrophages) as Trojan horses to spread in the host. Inflammatory reaction only appears when the parasite bursts infected cells. Immunity against extracellular parasites is depicted for the myxozoans Ceratonova shasta and Enteromyxum spp. The cellular and humoral innate responses and the production of antibodies are crucial for resolving some of these myxozoonoses, but an excessive inflammatory reaction (concerted by cytokines) can become a fatal pathophysiological consequence. The local immune response plays a key role, with numerous genes more strongly regulated in the intestine than at lymphohaematopoietic organs.
Topics: Animals; Apicomplexa; Fishes; Gastrointestinal Tract; Immune Evasion; Immunity, Innate; Inflammation; Microsporidia; Microsporidiosis; Myxozoa; Parasitic Diseases, Animal; Protozoan Infections
PubMed: 26828391
DOI: 10.1016/j.dci.2016.01.014 -
PLoS Pathogens Nov 2016Microsporidia are strict obligate intracellular parasites that infect a wide range of eukaryotes including humans and economically important fish and insects. Surviving... (Review)
Review
Microsporidia are strict obligate intracellular parasites that infect a wide range of eukaryotes including humans and economically important fish and insects. Surviving and flourishing inside another eukaryotic cell is a very specialised lifestyle that requires evolutionary innovation. Genome sequence analyses show that microsporidia have lost most of the genes needed for making primary metabolites, such as amino acids and nucleotides, and also that they have only a limited capacity for making adenosine triphosphate (ATP). Since microsporidia cannot grow and replicate without the enormous amounts of energy and nucleotide building blocks needed for protein, DNA, and RNA biosynthesis, they must have evolved ways of stealing these substrates from the infected host cell. Providing they can do this, genome analyses suggest that microsporidia have the enzyme repertoire needed to use and regenerate the imported nucleotides efficiently. Recent functional studies suggest that a critical innovation for adapting to intracellular life was the acquisition by lateral gene transfer of nucleotide transport (NTT) proteins that are now present in multiple copies in all microsporidian genomes. These proteins are expressed on the parasite surface and allow microsporidia to steal ATP and other purine nucleotides for energy and biosynthesis from their host. However, it remains unclear how other essential metabolites, such as pyrimidine nucleotides, are acquired. Transcriptomic and experimental studies suggest that microsporidia might manipulate host cell metabolism and cell biological processes to promote nucleotide synthesis and to maximise the potential for ATP and nucleotide import. In this review, we summarise recent genomic and functional data relating to how microsporidia exploit their hosts for energy and building blocks needed for growth and nucleic acid metabolism and we identify some remaining outstanding questions.
Topics: Animals; Host-Parasite Interactions; Humans; Microsporidia; Nucleotides
PubMed: 27855212
DOI: 10.1371/journal.ppat.1005870 -
Experientia Supplementum (2012) 2022Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia... (Review)
Review
Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology. Here we review results about microsporidia infections in C. elegans, which began with the discovery of the intestinal-infecting species Nematocida parisii. Recent findings include new species identification in the Nematocida genus, with more intestinal-infecting species, and also a species with broader tissue tropism, the epidermal and muscle-infecting species Nematocida displodere. This species has a longer polar tube infection apparatus, which may enable its wider tissue range. After invasion, multiple Nematocida species appear to fuse host cells, which likely promotes their dissemination within host organs. Localized proteomics identified Nematocida proteins that have direct contact with the C. elegans intestinal cytosol and nucleus, and many of these host-exposed proteins belong to expanded, species-specific gene families. On the host side, forward genetic screens have identified regulators of the Intracellular Pathogen Response (IPR), which is a transcriptional response induced by both microsporidia and the Orsay virus, which is also a natural, obligate intracellular pathogen of the C. elegans intestine. The IPR constitutes a novel immune/stress response that promotes resistance against microsporidia, virus, and heat shock. Overall, the Nematocida/C. elegans system has provided insights about strategies for microsporidia pathogenesis, as well as innate defense pathways against these parasites.
Topics: Animals; Biology; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Host-Pathogen Interactions; Microsporidia
PubMed: 35544001
DOI: 10.1007/978-3-030-93306-7_5 -
The Journal of Veterinary Medical... Feb 2016Microsporidia are obligate intracellular mitochondria-lacking pathogens that rely on host cells to grow and multiply. Microsporidia, currently classified as fungi, are... (Review)
Review
Microsporidia are obligate intracellular mitochondria-lacking pathogens that rely on host cells to grow and multiply. Microsporidia, currently classified as fungi, are ubiquitous in nature and are found worldwide. They infect a large number of mammals and are recognized as opportunistic infection agents in HIV-AIDS patients. Its importance for veterinary medicine has been unveiled in recent years through the description of clinical and subclinical forms of infection in domestic and wild animals. Domestic and wild birds may be infected by the same human microsporidia, reinforcing their zoonotic potential. Microsporidiosis in fish is prevalent and causes significant economic losses for fish farming. Some species of microsporidia have been propagated in cell cultures, which may provide conditions for the development of diagnostic techniques, understanding of pathogenesis and immune responses and for the discovery of potential therapies. Unfortunately, the cultivation of these parasites is not fully standardized in most research laboratories, especially in the veterinary field. The aim of this review is to relate the most important microsporidia of veterinary interest and demonstrate how these pathogens can be grown and propagated in cell culture for diagnostic purposes or for pathogenesis studies. Cultivation of microsporidia allowed the study of its life cycle, metabolism, pathogenesis and diagnosis, and may also serve as a repository for these pathogens for molecular, biochemical, antigenic and epidemiological studies.
Topics: Animals; Humans; Microsporidia; Microsporidiosis; Mycology; Veterinary Medicine
PubMed: 26346746
DOI: 10.1292/jvms.15-0401