''Encephalitozoon cuniculi'' (''E. cuniculi'') is a

mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

with world-wide distribution. An important cause of

neurologic Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...

and

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

disease in rabbits, ''E. cuniculi'' can also cause disease in

immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

people.

Classification and cell structure

''E. cuniculi'' is a

spore In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...

-forming

unicellular A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells. Organisms fall into two general categories: prokaryotic organisms and ...

parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...

belonging to the phylum

Microsporidia Microsporidia are a group of spore-forming unicellular parasites. These spores contain an extrusion apparatus that has a coiled polar tube ending in an anchoring disc at the apical part of the spore. They were once considered protozoans or prot ...

. Microsporidia are obligate intracellular parasitic fungi infecting many animal groups. Lacking

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and

peroxysome A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...

s, these

eukaryotes were first considered a deeply branching

protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the exc ...

lineage that diverged before the

endosymbiotic event An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualism (biology), mutualistic relationship. (The term endosymbiosis is from the Greek language, G ...

that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular

phylogenetic In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...

data later implied that microsporidia are atypical fungi that lost mitochondria during evolution.

Genome

The

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

consists of approximately 2.9-

megabase A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s (Mbs) in 11

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

s, with a total of 1,997 potential

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

-coding

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s. Genome compaction is reflected by reduced

intergenic spacer Spacer DNA is a region of non-coding DNA between genes. The terms intergenic spacer (IGS) or non-transcribed spacer (NTS) are used particularly for the spacer DNA between the many tandemly repeated copies of the ribosomal RNA genes. In bacteria, ...

s and by the shortness of most putative proteins relative to their eukaryote

orthologue Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...

s. At the time of publication (2001), only 44% of the proteins had a function assigned to them. the latest reference proteome in Uniprot (2021) lists 2041 proteins with ~620 proteins annotated as "uncharacterized", about 200 without annotation (e.g. "UPF0329 protei
ECU06_1620
) and another ~150 or so that are annotated as having some "

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

" (including

domains of unknown function A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of ...

) and numerous proteins of "probable" and "putative" function plus dozens with "similarity" to characterized proteins. Hence, even 20 years after the genome sequence was published, about 50% of the ''E. cuniculi'' proteome remains uncharacterized or poorly understood. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the

tricarboxylic acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...

. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the ''E. cuniculi'' genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), it is possible that microsporidia have retained a mitochondrion-derived organelle.

Life cycle and pathogenesis

The infective form of microsporidia (''E. cuniculi'') is a resistant

which can survive for a long time in the environment. The spore extrudes its polar tubule and infects the host cell. The spore injects the infective

sporoplasm Sporoplasm is an infectious material present in the cytoplasm of various fungi-like organisms, such as members of class ''Microsporidia''. Sporoplasm is defined as a mass of protoplasm that gives rise to or forms a spore. The protoplasmic body t ...

into the eukaryotic host cell through a polar tube. Inside the cell, the sporoplasm undergoes extensive multiplication. This multiplication occurs either by

merogony Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...

(binary fission) or

schizogony Fission, in biology, is the division of a single entity into two or more parts and the regeneration of those parts to separate entities resembling the original. The object experiencing fission is usually a cell, but the term may also refer to how ...

(multiple fission). Microsporidia develop by sporogony to mature spores in the cytoplasm or inside

parasitophorous vacuole The parasitophorous vacuole (PV) is a structure produced by apicomplexan parasites in the cells of its host. The PV allows the parasite to develop while protected from the phagolysosomes of the host cell. The PV is a bubble-like compartment mad ...

. During sporogony, a thick wall is formed around the spore. The thick wall formed provides resistance to adverse environmental conditions. Once the spores increase in number and completely fill the cytoplasm of the host's cell, the cell membrane is disrupted and releases the spores to the surroundings. These free mature spores can infect new cells thus continuing the cycle.

Epidemiology

First identified in rabbits, ''E. cuniculi'' infections have been reported worldwide in over 20 mammalian species, including humans.

Prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

in pet rabbits is high, with 23-75% having

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

to the disease. Studies of healthy dogs have found a 0-38% prevalence. Cats appear to be relatively resistant to the organism, although experimental infections in kittens with

feline leukemia virus Feline leukemia virus (FeLV) is a retrovirus that infects cats. FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's immune system, the virus weakens the cat's i ...

have been described. ''E. cuniculi'' also infects rodents, and the organism has been detected in the feces of 13% of pet birds. A small percentage of healthy people have antibodies to the organism, indicating previous exposure. Seroprevalence rates are higher in immunocompromised people, and in those who live in or have visited tropical countries. Most infections do not result in clinical disease. ''E. cuniculi'' spores are usually shed in urine, but can also be found in the feces and respiratory secretions of infected animals. Spores can be detected in urine 38-63 days after infection, with intermittent shedding thereafter. Ingestion of spores is the main route of transmission, although inhalation of spores can also occur.

Transplacental {{Short pages monitor